chr20-6075049-GTTTTTT-G

Variant names:

• chr20-6075049-GTTTTTT-G
• rs11405989
• ENST00000478194.1:n.3112_3117delAAAAAA

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The ENST00000478194.1(FERMT1):​n.3112_3117delAAAAAA 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 0.00118 in 129,150 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0012 (0 hom., cov: 22)
• Consequence: FERMT1 ENST00000478194.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214
• 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: Likely_benign. The variant received -4 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00118 (153/129150) while in subpopulation AFR AF = 0.00451 (139/30804). AF 95% confidence interval is 0.0039. There are 0 homozygotes in GnomAd4. There are 79 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FERMT1	NM_017671.5	c.*2118_*2123delAAAAAA		3_prime_UTR_variant	Exon 15 of 15	ENST00000217289.9	NP_060141.3
FERMT1	XM_024451935.2	c.*2118_*2123delAAAAAA		3_prime_UTR_variant	Exon 15 of 15		XP_024307703.1
FERMT1	XM_047440259.1	c.*2118_*2123delAAAAAA		3_prime_UTR_variant	Exon 15 of 15		XP_047296215.1
FERMT1	XM_047440260.1	c.*2118_*2123delAAAAAA		3_prime_UTR_variant	Exon 14 of 14		XP_047296216.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FERMT1	ENST00000478194.1	n.3112_3117delAAAAAA		non_coding_transcript_exon_variant	Exon 7 of 7	1
FERMT1	ENST00000217289.9	c.*2118_*2123delAAAAAA		3_prime_UTR_variant	Exon 15 of 15	1	NM_017671.5	ENSP00000217289.4

Frequencies

GnomAD3 genomes AF: 0.00118 AC: 152 AN: 129134 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00449

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000812

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000159

Gnomad OTH AF: 0.00113

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

GnomAD4 genome AF: 0.00118 AC: 153 AN: 129150 Hom.: 0 Cov.: 22 AF XY: 0.00127 AC XY: 79 AN XY: 62130

African (AFR) AF: 0.00451 AC: 139 AN: 30804

American (AMR) AF: 0.000810 AC: 11 AN: 13572

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3104

East Asian (EAS) AF: 0.00 AC: 0 AN: 4694

South Asian (SAS) AF: 0.00 AC: 0 AN: 4224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7148

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 244

European-Non Finnish (NFE) AF: 0.0000159 AC: 1 AN: 62736

Other (OTH) AF: 0.00112 AC: 2 AN: 1782

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.21

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11405989; hg19: chr20-6055696;