Genetic Variant FERMT1:c.*1885G>A (chr20-6075288-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting

The NM_017671.5(FERMT1):c.*1885G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00144 in 152,040 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FERMT1
NM_017671.5 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.675

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

Kindler syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics

FERMT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00144 (219/152040) while in subpopulation AFR AF = 0.00497 (206/41472). AF 95% confidence interval is 0.00441. There are 1 homozygotes in GnomAd4. There are 95 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017671.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FERMT1	NM_017671.5	MANE Select	c.*1885G>A		3_prime_UTR	Exon 15 of 15	NP_060141.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FERMT1	ENST00000217289.9	TSL:1 MANE Select	c.*1885G>A	3_prime_UTR	Exon 15 of 15	ENSP00000217289.4	Q9BQL6-1
FERMT1	ENST00000478194.1	TSL:1	n.2879G>A	non_coding_transcript_exon	Exon 7 of 7
FERMT1	ENST00000855451.1		c.*1885G>A	3_prime_UTR	Exon 15 of 15	ENSP00000525510.1

Frequencies

GnomAD3 genomes

AF:

0.00144

AC:

219

AN:

151922

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00498

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000525

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00191

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

138

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

138

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.00144

AC:

219

AN:

152040

Hom.:

Cov.:

AF XY:

0.00128

AC XY:

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.00497

AC:

206

AN:

41472

American (AMR)

AF:

0.000524

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.000208

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10552

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67982

Other (OTH)

AF:

0.00189

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00149

Hom.:

Bravo

AF:

0.00172

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Kindler syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.4

(source)

DANN

Benign

0.57

PhyloP100

-0.68

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over