rs10373

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_017671.5(FERMT1):c.114T>C(p.His38His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 1,613,046 control chromosomes in the GnomAD database, including 226,414 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 20867 hom., cov: 33)

Exomes 𝑓: 0.53 ( 205547 hom. )

Consequence

FERMT1
NM_017671.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.140

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=-0.82).

BP6

Variant 20-6119441-A-G is Benign according to our data. Variant chr20-6119441-A-G is described in ClinVar as [Benign]. Clinvar id is 260864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.14 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FERMT1	NM_017671.5 link	c.114T>C	p.His38His	synonymous_variant	Exon 2 of 15	ENST00000217289.9	NP_060141.3	Q9BQL6-1Q54A15Q49AC8
FERMT1	XM_024451935.2 link	c.114T>C	p.His38His	synonymous_variant	Exon 2 of 15		XP_024307703.1
FERMT1	XM_047440259.1 link	c.114T>C	p.His38His	synonymous_variant	Exon 2 of 15		XP_047296215.1
FERMT1	XM_047440260.1 link	c.-155T>C		5_prime_UTR_variant	Exon 1 of 14		XP_047296216.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FERMT1	ENST00000217289.9 link	c.114T>C	p.His38His	synonymous_variant	Exon 2 of 15	1	NM_017671.5	ENSP00000217289.4		Q9BQL6-1

Frequencies

GnomAD3 genomes

AF:

0.521

AC:

79162

AN:

151960

Hom.:

20867

Cov.:

show subpopulations

Gnomad AFR

AF:

0.537

Gnomad AMI

AF:

0.567

Gnomad AMR

AF:

0.496

Gnomad ASJ

AF:

0.610

Gnomad EAS

AF:

0.380

Gnomad SAS

AF:

0.642

Gnomad FIN

AF:

0.414

Gnomad MID

AF:

0.639

Gnomad NFE

AF:

0.529

Gnomad OTH

AF:

0.545

GnomAD3 exomes

AF:

0.520

AC:

130603

AN:

251378

Hom.:

34696

AF XY:

0.530

AC XY:

72030

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.534

Gnomad AMR exome

AF:

0.463

Gnomad ASJ exome

AF:

0.613

Gnomad EAS exome

AF:

0.379

Gnomad SAS exome

AF:

0.659

Gnomad FIN exome

AF:

0.419

Gnomad NFE exome

AF:

0.529

Gnomad OTH exome

AF:

0.546

GnomAD4 exome

AF:

0.527

AC:

770633

AN:

1460972

Hom.:

205547

Cov.:

AF XY:

0.532

AC XY:

386474

AN XY:

726796

show subpopulations

Gnomad4 AFR exome

AF:

0.544

Gnomad4 AMR exome

AF:

0.465

Gnomad4 ASJ exome

AF:

0.612

Gnomad4 EAS exome

AF:

0.374

Gnomad4 SAS exome

AF:

0.652

Gnomad4 FIN exome

AF:

0.424

Gnomad4 NFE exome

AF:

0.528

Gnomad4 OTH exome

AF:

0.529

GnomAD4 genome

AF:

0.521

AC:

79180

AN:

152074

Hom.:

20867

Cov.:

AF XY:

0.516

AC XY:

38382

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.536

Gnomad4 AMR

AF:

0.496

Gnomad4 ASJ

AF:

0.610

Gnomad4 EAS

AF:

0.380

Gnomad4 SAS

AF:

0.642

Gnomad4 FIN

AF:

0.414

Gnomad4 NFE

AF:

0.529

Gnomad4 OTH

AF:

0.538

Alfa

AF:

0.533

Hom.:

28717

Bravo

AF:

0.524

Asia WGS

AF:

0.471

AC:

1641

AN:

3478

EpiCase

AF:

0.538

EpiControl

AF:

0.549

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:2

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 76% of patients studied by a panel of primary immunodeficiencies. Number of patients: 67. Only high quality variants are reported. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Kindler syndrome

Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.4

DANN

Benign

0.38

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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