Genetic Variant FERMT1:c.*2016T>A (chr20-6075157-A-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017671.5(FERMT1):c.*2016T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0449 in 152,238 control chromosomes in the GnomAD database, including 305 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.045 ( 305 hom., cov: 31)

Exomes 𝑓: 0.022 ( 0 hom. )

Consequence

FERMT1
NM_017671.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.474

Publications

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

FERMT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 20-6075157-A-T is Benign according to our data. Variant chr20-6075157-A-T is described in ClinVar as Benign. ClinVar VariationId is 339177.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017671.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FERMT1	NM_017671.5	MANE Select	c.*2016T>A		3_prime_UTR	Exon 15 of 15	NP_060141.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FERMT1	ENST00000217289.9	TSL:1 MANE Select	c.*2016T>A	3_prime_UTR	Exon 15 of 15	ENSP00000217289.4	Q9BQL6-1
FERMT1	ENST00000478194.1	TSL:1	n.3010T>A	non_coding_transcript_exon	Exon 7 of 7
FERMT1	ENST00000855451.1		c.*2016T>A	3_prime_UTR	Exon 15 of 15	ENSP00000525510.1

Frequencies

GnomAD3 genomes

AF:

0.0447

AC:

6801

AN:

151982

Hom.:

303

Cov.:

show subpopulations

Gnomad AFR

AF:

0.107

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0326

Gnomad ASJ

AF:

0.0358

Gnomad EAS

AF:

0.00813

Gnomad SAS

AF:

0.102

Gnomad FIN

AF:

0.00189

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0159

Gnomad OTH

AF:

0.0513

GnomAD4 exome

AF:

0.0217

AC:

AN:

138

Hom.:

Cov.:

AF XY:

0.0132

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.0217

AC:

AN:

138

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:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0449

AC:

6828

AN:

152100

Hom.:

305

Cov.:

AF XY:

0.0457

AC XY:

3400

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.107

AC:

4450

AN:

41458

American (AMR)

AF:

0.0325

AC:

496

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.0358

AC:

124

AN:

3468

East Asian (EAS)

AF:

0.00815

AC:

AN:

5156

South Asian (SAS)

AF:

0.102

AC:

491

AN:

4812

European-Finnish (FIN)

AF:

0.00189

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0159

AC:

1078

AN:

68008

Other (OTH)

AF:

0.0517

AC:

109

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

316

632

947

1263

1579

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

258

344

430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0312

Hom.:

Bravo

AF:

0.0479

Asia WGS

AF:

0.0510

AC:

178

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Kindler syndrome (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

4.8

(source)

DANN

Benign

0.84

PhyloP100

0.47

Mutation Taster

=100/0

polymorphism (auto)

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over