20-6075049-G-GT

Position:

• chr20-6075049-G-GT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_017671.5(FERMT1):​c.*2123_*2124insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 129,034 control chromosomes in the GnomAD database, including 1,956 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (1956 hom., cov: 22)
  • Exomes 𝑓: 0.14 (0 hom.)
• Consequence: FERMT1 NM_017671.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 0.184

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 Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FERMT1	NM_017671.5	c.*2123_*2124insA		3_prime_UTR_variant	15/15	ENST00000217289.9
FERMT1	XM_024451935.2	c.*2123_*2124insA		3_prime_UTR_variant	15/15
FERMT1	XM_047440259.1	c.*2123_*2124insA		3_prime_UTR_variant	15/15
FERMT1	XM_047440260.1	c.*2123_*2124insA		3_prime_UTR_variant	14/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FERMT1	ENST00000217289.9	c.*2123_*2124insA		3_prime_UTR_variant	15/15	1	NM_017671.5	P1
FERMT1	ENST00000478194.1	n.3117_3118insA		non_coding_transcript_exon_variant	7/7	1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 21527 AN: 128952 Hom.: 1954 Cov.: 22

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.00935

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.116

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.138

GnomAD4 exome AF: 0.136 AC: 9 AN: 66 Hom.: 0 Cov.: 0 AF XY: 0.194 AC XY: 7 AN XY: 36

Gnomad4 EAS exome AF: 0.136

GnomAD4 genome AF: 0.167 AC: 21532 AN: 128968 Hom.: 1956 Cov.: 22 AF XY: 0.168 AC XY: 10440 AN XY: 62024

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.195

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.00938

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.197

Gnomad4 OTH AF: 0.136

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Kindler syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

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: rs11405989; hg19: chr20-6055696;