rs753927

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_017671.5(FERMT1):c.1695T>C(p.Phe565=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 1,612,042 control chromosomes in the GnomAD database, including 110,378 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 10836 hom., cov: 33)

Exomes 𝑓: 0.36 ( 99542 hom. )

Consequence

FERMT1
NM_017671.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.118

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 20-6084063-A-G is Benign according to our data. Variant chr20-6084063-A-G is described in ClinVar as [Benign]. Clinvar id is 260868.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-6084063-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.118 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
FERMT1	NM_017671.5 linkuse as main transcript	c.1695T>C	p.Phe565=	synonymous_variant	13/15	ENST00000217289.9	NP_060141.3
FERMT1	XM_024451935.2 linkuse as main transcript	c.1695T>C	p.Phe565=	synonymous_variant	13/15		XP_024307703.1
FERMT1	XM_047440259.1 linkuse as main transcript	c.1695T>C	p.Phe565=	synonymous_variant	13/15		XP_047296215.1
FERMT1	XM_047440260.1 linkuse as main transcript	c.1410T>C	p.Phe470=	synonymous_variant	12/14		XP_047296216.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FERMT1	ENST00000217289.9 linkuse as main transcript	c.1695T>C	p.Phe565=	synonymous_variant	13/15	1	NM_017671.5	ENSP00000217289	P1	Q9BQL6-1
FERMT1	ENST00000478194.1 linkuse as main transcript	n.655T>C		non_coding_transcript_exon_variant	5/7	1
FERMT1	ENST00000536936.1 linkuse as main transcript	c.*1197T>C		3_prime_UTR_variant, NMD_transcript_variant	12/14	1		ENSP00000441063
FERMT1	ENST00000699095.1 linkuse as main transcript	c.1695T>C	p.Phe565=	synonymous_variant	12/14			ENSP00000514127	P1	Q9BQL6-1

Frequencies

GnomAD3 genomes

AF:

0.370

AC:

56313

AN:

152038

Hom.:

10824

Cov.:

show subpopulations

Gnomad AFR

AF:

0.351

Gnomad AMI

AF:

0.416

Gnomad AMR

AF:

0.456

Gnomad ASJ

AF:

0.371

Gnomad EAS

AF:

0.617

Gnomad SAS

AF:

0.283

Gnomad FIN

AF:

0.273

Gnomad MID

AF:

0.386

Gnomad NFE

AF:

0.365

Gnomad OTH

AF:

0.387

GnomAD3 exomes

AF:

0.376

AC:

94290

AN:

250470

Hom.:

18941

AF XY:

0.367

AC XY:

49616

AN XY:

135348

show subpopulations

Gnomad AFR exome

AF:

0.342

Gnomad AMR exome

AF:

0.488

Gnomad ASJ exome

AF:

0.380

Gnomad EAS exome

AF:

0.630

Gnomad SAS exome

AF:

0.274

Gnomad FIN exome

AF:

0.271

Gnomad NFE exome

AF:

0.355

Gnomad OTH exome

AF:

0.366

GnomAD4 exome

AF:

0.363

AC:

530625

AN:

1459886

Hom.:

99542

Cov.:

AF XY:

0.361

AC XY:

262202

AN XY:

726364

show subpopulations

Gnomad4 AFR exome

AF:

0.344

Gnomad4 AMR exome

AF:

0.482

Gnomad4 ASJ exome

AF:

0.373

Gnomad4 EAS exome

AF:

0.636

Gnomad4 SAS exome

AF:

0.275

Gnomad4 FIN exome

AF:

0.274

Gnomad4 NFE exome

AF:

0.360

Gnomad4 OTH exome

AF:

0.372

GnomAD4 genome

AF:

0.370

AC:

56353

AN:

152156

Hom.:

10836

Cov.:

AF XY:

0.370

AC XY:

27486

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.350

Gnomad4 AMR

AF:

0.456

Gnomad4 ASJ

AF:

0.371

Gnomad4 EAS

AF:

0.619

Gnomad4 SAS

AF:

0.281

Gnomad4 FIN

AF:

0.273

Gnomad4 NFE

AF:

0.365

Gnomad4 OTH

AF:

0.393

Alfa

AF:

0.373

Hom.:

20281

Bravo

AF:

0.387

Asia WGS

AF:

0.445

AC:

1548

AN:

3478

EpiCase

AF:

0.372

EpiControl

AF:

0.363

ClinVar

Significance: Benign

Submissions summary: Benign:5

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 72% of patients studied by a panel of primary immunodeficiencies. Number of patients: 63. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Kindler syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

1.2

DANN

Benign

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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