Genetic Variant FERMT1:n.3117delA (chr20-6075049-GT-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000478194.1(FERMT1):n.3117delA 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 0.0237 in 129,168 control chromosomes in the GnomAD database, including 47 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.024 ( 47 hom., cov: 22)

Exomes 𝑓: 0.078 ( 0 hom. )

Consequence

FERMT1
ENST00000478194.1 non_coding_transcript_exon

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.184

Publications

0 publications found

Variant links:

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

FERMT1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
FERMT1	NM_017671.5 link	c.*2123delA	3_prime_UTR_variant	Exon 15 of 15	ENST00000217289.9	NP_060141.3	Q9BQL6-1Q54A15Q49AC8
FERMT1	XM_024451935.2 link	c.*2123delA	3_prime_UTR_variant	Exon 15 of 15		XP_024307703.1
FERMT1	XM_047440259.1 link	c.*2123delA	3_prime_UTR_variant	Exon 15 of 15		XP_047296215.1
FERMT1	XM_047440260.1 link	c.*2123delA	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 link	n.3117delA		non_coding_transcript_exon_variant	Exon 7 of 7	1
FERMT1	ENST00000217289.9 link	c.*2123delA		3_prime_UTR_variant	Exon 15 of 15	1	NM_017671.5	ENSP00000217289.4		Q9BQL6-1

Frequencies

GnomAD3 genomes

AF:

0.0237

AC:

3053

AN:

129088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0486

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0190

Gnomad ASJ

AF:

0.0313

Gnomad EAS

AF:

0.00149

Gnomad SAS

AF:

0.0567

Gnomad FIN

AF:

0.00350

Gnomad MID

AF:

0.0224

Gnomad NFE

AF:

0.0140

Gnomad OTH

AF:

0.0249

GnomAD4 exome

AF:

0.0781

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0833

AC XY:

AN XY:

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.0781

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.305

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0236

AC:

3053

AN:

129104

Hom.:

Cov.:

AF XY:

0.0239

AC XY:

1485

AN XY:

62112

show subpopulations

African (AFR)

AF:

0.0487

AC:

1499

AN:

30794

American (AMR)

AF:

0.0190

AC:

258

AN:

13568

Ashkenazi Jewish (ASJ)

AF:

0.0313

AC:

AN:

3102

East Asian (EAS)

AF:

0.00149

AC:

AN:

4692

South Asian (SAS)

AF:

0.0566

AC:

239

AN:

4226

European-Finnish (FIN)

AF:

0.00350

AC:

AN:

7144

Middle Eastern (MID)

AF:

0.0246

AC:

AN:

244

European-Non Finnish (NFE)

AF:

0.0140

AC:

878

AN:

62712

Other (OTH)

AF:

0.0247

AC:

AN:

1780

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

140

280

421

561

701

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.18

Mutation Taster

=100/0

polymorphism

(source)

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

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chr20-6075049-GT-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over