rs17224644

Positions:

• chr20-6094102-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017671.5(FERMT1):​c.1139+837C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0945 in 152,224 control chromosomes in the GnomAD database, including 812 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.095 (812 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: FERMT1 NM_017671.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.330

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 20-6094102-G-A is Benign according to our data. Variant chr20-6094102-G-A is described in ClinVar as [Benign]. Clinvar id is 1237052.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FERMT1	NM_017671.5	c.1139+837C>T		intron_variant		ENST00000217289.9	NP_060141.3
FERMT1	XM_024451935.2	c.1139+837C>T		intron_variant			XP_024307703.1
FERMT1	XM_047440259.1	c.1139+837C>T		intron_variant			XP_047296215.1
FERMT1	XM_047440260.1	c.854+837C>T		intron_variant			XP_047296216.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FERMT1	ENST00000217289.9	c.1139+837C>T		intron_variant		1	NM_017671.5	ENSP00000217289.4

Frequencies

GnomAD3 genomes AF: 0.0946 AC: 14389 AN: 152106 Hom.: 811 Cov.: 33

Gnomad AFR AF: 0.0454

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0963

Gnomad FIN AF: 0.0607

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.124

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0945 AC: 14391 AN: 152224 Hom.: 812 Cov.: 33 AF XY: 0.0913 AC XY: 6796 AN XY: 74442

Gnomad4 AFR AF: 0.0457

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0955

Gnomad4 FIN AF: 0.0607

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.122

Alfa AF: 0.104 Hom.: 154

Bravo AF: 0.0959

Asia WGS AF: 0.0330 AC: 114 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.0
DANN	Benign	0.89

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: rs17224644; hg19: chr20-6074749;