20-6075045-G-GT

Position:

• chr20-6075045-G-GT

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_Supporting BS2

The NM_017671.5(FERMT1):​c.*2127_*2128insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00134 in 133,236 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (4 hom., cov: 31)
  • Exomes 𝑓: 0.0079 (0 hom.)
• Consequence: FERMT1 NM_017671.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.90

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]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00134 (178/133110) while in subpopulation EAS AF= 0.00771 (36/4668). AF 95% confidence interval is 0.00573. There are 4 homozygotes in gnomad4. There are 93 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FERMT1	NM_017671.5	c.*2127_*2128insA		3_prime_UTR_variant	15/15	ENST00000217289.9
FERMT1	XM_024451935.2	c.*2127_*2128insA		3_prime_UTR_variant	15/15
FERMT1	XM_047440259.1	c.*2127_*2128insA		3_prime_UTR_variant	15/15
FERMT1	XM_047440260.1	c.*2127_*2128insA		3_prime_UTR_variant	14/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FERMT1	ENST00000217289.9	c.*2127_*2128insA		3_prime_UTR_variant	15/15	1	NM_017671.5	P1
FERMT1	ENST00000478194.1	n.3121_3122insA		non_coding_transcript_exon_variant	7/7	1

Frequencies

GnomAD3 genomes AF: 0.00134 AC: 178 AN: 133072 Hom.: 4 Cov.: 31

Gnomad AFR AF: 0.000696

Gnomad AMI AF: 0.00694

Gnomad AMR AF: 0.00199

Gnomad ASJ AF: 0.000917

Gnomad EAS AF: 0.00790

Gnomad SAS AF: 0.00192

Gnomad FIN AF: 0.000551

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00107

Gnomad OTH AF: 0.00162

GnomAD4 exome AF: 0.00794 AC: 1 AN: 126 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 68

Gnomad4 EAS exome AF: 0.00794

GnomAD4 genome AF: 0.00134 AC: 178 AN: 133110 Hom.: 4 Cov.: 31 AF XY: 0.00145 AC XY: 93 AN XY: 64272

Gnomad4 AFR AF: 0.000694

Gnomad4 AMR AF: 0.00199

Gnomad4 ASJ AF: 0.000917

Gnomad4 EAS AF: 0.00771

Gnomad4 SAS AF: 0.00192

Gnomad4 FIN AF: 0.000551

Gnomad4 NFE AF: 0.00107

Gnomad4 OTH AF: 0.00215

Alfa AF: 0.000491 Hom.: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Kindler syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs139990090; hg19: chr20-6055692;