rs6516104

Variant names:

• chr20-6108866-C-T
• rs6516104
• NM_017671.5:c.747-1232G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017671.5(FERMT1):​c.747-1232G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 151,138 control chromosomes in the GnomAD database, including 2,067 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.14 (2067 hom., cov: 30)
• Consequence: FERMT1 NM_017671.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52
• Publications: 4 publications found

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: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FERMT1	NM_017671.5	c.747-1232G>A		intron_variant	Intron 5 of 14	ENST00000217289.9	NP_060141.3
FERMT1	XM_024451935.2	c.747-1232G>A		intron_variant	Intron 5 of 14		XP_024307703.1
FERMT1	XM_047440259.1	c.747-1232G>A		intron_variant	Intron 5 of 14		XP_047296215.1
FERMT1	XM_047440260.1	c.462-1232G>A		intron_variant	Intron 4 of 13		XP_047296216.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FERMT1	ENST00000217289.9	c.747-1232G>A		intron_variant	Intron 5 of 14	1	NM_017671.5	ENSP00000217289.4

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21488 AN: 151062 Hom.: 2063 Cov.: 30

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.0969

Gnomad AMR AF: 0.0891

Gnomad ASJ AF: 0.0692

Gnomad EAS AF: 0.0779

Gnomad SAS AF: 0.0540

Gnomad FIN AF: 0.0899

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.0982

Gnomad OTH AF: 0.114

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.142 AC: 21523 AN: 151138 Hom.: 2067 Cov.: 30 AF XY: 0.140 AC XY: 10357 AN XY: 73770

African (AFR) AF: 0.276 AC: 11318 AN: 41072

American (AMR) AF: 0.0890 AC: 1354 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.0692 AC: 240 AN: 3466

East Asian (EAS) AF: 0.0783 AC: 403 AN: 5146

South Asian (SAS) AF: 0.0539 AC: 257 AN: 4764

European-Finnish (FIN) AF: 0.0899 AC: 929 AN: 10330

Middle Eastern (MID) AF: 0.106 AC: 31 AN: 292

European-Non Finnish (NFE) AF: 0.0982 AC: 6666 AN: 67860

Other (OTH) AF: 0.114 AC: 237 AN: 2086

Alfa AF: 0.128 Hom.: 309

Bravo AF: 0.149

Asia WGS AF: 0.0700 AC: 244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.88
DANN	Benign	0.47
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6516104; hg19: chr20-6089513;