rs2232074

Positions:

chr20-6085082-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017671.5(FERMT1):c.1577G>A(p.Arg526Lys) variant causes a missense change. The variant allele was found at a frequency of 0.385 in 1,611,632 control chromosomes in the GnomAD database, including 123,094 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 13259 hom., cov: 32)

Exomes 𝑓: 0.38 ( 109835 hom. )

Consequence

FERMT1
NM_017671.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 6.21

Variant links:

Genes affected

FERMT1 (HGNC:15889): (FERM domain containing kindlin 1) This gene encodes a member of the fermitin family, and contains a FERM domain and a pleckstrin homology domain. The encoded protein is involved in integrin signaling and linkage of the actin cytoskeleton to the extracellular matrix. Mutations in this gene have been linked to Kindler syndrome. [provided by RefSeq, Dec 2009]

FERMT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.15422E-5).

BP6

Variant 20-6085082-C-T is Benign according to our data. Variant chr20-6085082-C-T is described in ClinVar as [Benign]. Clinvar id is 260867.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-6085082-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
FERMT1	NM_017671.5 linkuse as main transcript	c.1577G>A	p.Arg526Lys	missense_variant	12/15	ENST00000217289.9
FERMT1	XM_024451935.2 linkuse as main transcript	c.1577G>A	p.Arg526Lys	missense_variant	12/15
FERMT1	XM_047440259.1 linkuse as main transcript	c.1577G>A	p.Arg526Lys	missense_variant	12/15
FERMT1	XM_047440260.1 linkuse as main transcript	c.1292G>A	p.Arg431Lys	missense_variant	11/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FERMT1	ENST00000217289.9 linkuse as main transcript	c.1577G>A	p.Arg526Lys	missense_variant	12/15	1	NM_017671.5	P1	Q9BQL6-1
FERMT1	ENST00000478194.1 linkuse as main transcript	n.537G>A		non_coding_transcript_exon_variant	4/7	1
FERMT1	ENST00000536936.1 linkuse as main transcript	c.*1079G>A		3_prime_UTR_variant, NMD_transcript_variant	11/14	1
FERMT1	ENST00000699095.1 linkuse as main transcript	c.1577G>A	p.Arg526Lys	missense_variant	11/14			P1	Q9BQL6-1

Frequencies

GnomAD3 genomes

AF:

0.412

AC:

62446

AN:

151540

Hom.:

13241

Cov.:

show subpopulations

Gnomad AFR

AF:

0.458

Gnomad AMI

AF:

0.404

Gnomad AMR

AF:

0.483

Gnomad ASJ

AF:

0.420

Gnomad EAS

AF:

0.638

Gnomad SAS

AF:

0.336

Gnomad FIN

AF:

0.273

Gnomad MID

AF:

0.433

Gnomad NFE

AF:

0.377

Gnomad OTH

AF:

0.437

GnomAD3 exomes

AF:

0.404

AC:

101608

AN:

251378

Hom.:

21745

AF XY:

0.395

AC XY:

53598

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.456

Gnomad AMR exome

AF:

0.506

Gnomad ASJ exome

AF:

0.431

Gnomad EAS exome

AF:

0.651

Gnomad SAS exome

AF:

0.328

Gnomad FIN exome

AF:

0.273

Gnomad NFE exome

AF:

0.370

Gnomad OTH exome

AF:

0.393

GnomAD4 exome

AF:

0.383

AC:

558558

AN:

1459974

Hom.:

109835

Cov.:

AF XY:

0.381

AC XY:

276713

AN XY:

726422

show subpopulations

Gnomad4 AFR exome

AF:

0.458

Gnomad4 AMR exome

AF:

0.501

Gnomad4 ASJ exome

AF:

0.424

Gnomad4 EAS exome

AF:

0.648

Gnomad4 SAS exome

AF:

0.328

Gnomad4 FIN exome

AF:

0.276

Gnomad4 NFE exome

AF:

0.373

Gnomad4 OTH exome

AF:

0.402

GnomAD4 genome

AF:

0.412

AC:

62505

AN:

151658

Hom.:

13259

Cov.:

AF XY:

0.410

AC XY:

30397

AN XY:

74100

show subpopulations

Gnomad4 AFR

AF:

0.458

Gnomad4 AMR

AF:

0.483

Gnomad4 ASJ

AF:

0.420

Gnomad4 EAS

AF:

0.639

Gnomad4 SAS

AF:

0.334

Gnomad4 FIN

AF:

0.273

Gnomad4 NFE

AF:

0.377

Gnomad4 OTH

AF:

0.441

Alfa

AF:

0.396

Hom.:

18384

Bravo

AF:

0.434

TwinsUK

AF:

0.363

AC:

1345

ALSPAC

AF:

0.372

AC:

1434

ESP6500AA

AF:

0.0842

AC:

371

ESP6500EA

AF:

0.0516

AC:

444

ExAC

AF:

0.398

AC:

48296

Asia WGS

AF:

0.488

AC:

1695

AN:

3478

EpiCase

AF:

0.389

EpiControl

AF:

0.382

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 74% of patients studied by a panel of primary immunodeficiencies. Number of patients: 65. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Kindler syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.63

DEOGEN2

Benign

0.15

T;.

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.51

T;T

MetaRNN

Benign

0.000022

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-2.4

N;.

MutationTaster

Benign

0.70

P;P

PrimateAI

Uncertain

0.68

PROVEAN

Benign

2.4

N;N

REVEL

Benign

0.19

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;.

Vest4

0.089

MPC

0.26

ClinPred

0.017

GERP RS

5.2

Varity_R

0.076

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over