ENST00000478194.1:n.71C>T

Variant names:

• chr20-6094102-G-A
• rs17224644
• ENST00000478194.1:n.71C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000478194.1(FERMT1):​n.71C>T variant causes a non coding transcript exon 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 ENST00000478194.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.330
• Publications: 0 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 -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 VariationId 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 rank	MANE	Protein	UniProt
FERMT1	NM_017671.5	c.1139+837C>T		intron_variant	Intron 9 of 14	ENST00000217289.9	NP_060141.3
FERMT1	XM_024451935.2	c.1139+837C>T		intron_variant	Intron 9 of 14		XP_024307703.1
FERMT1	XM_047440259.1	c.1139+837C>T		intron_variant	Intron 9 of 14		XP_047296215.1
FERMT1	XM_047440260.1	c.854+837C>T		intron_variant	Intron 8 of 13		XP_047296216.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FERMT1	ENST00000217289.9	c.1139+837C>T		intron_variant	Intron 9 of 14	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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.0457 AC: 1896 AN: 41520

American (AMR) AF: 0.106 AC: 1617 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 701 AN: 3472

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5184

South Asian (SAS) AF: 0.0955 AC: 461 AN: 4826

European-Finnish (FIN) AF: 0.0607 AC: 643 AN: 10596

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8584 AN: 68010

Other (OTH) AF: 0.122 AC: 258 AN: 2114

Alfa AF: 0.102 Hom.: 155

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

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.0
DANN	Benign	0.89
PhyloP100		0.33
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: rs17224644; hg19: chr20-6074749;