Genetic Variant FAM13A:c.605+25827G>A (chr4-88965146-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014883.4(FAM13A):c.605+25827G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 151,982 control chromosomes in the GnomAD database, including 25,243 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

Frequency

Genomes: 𝑓 0.57 ( 25243 hom., cov: 31)

Consequence

FAM13A
NM_014883.4 intron

Scores

Clinical Significance

association no assertion criteria provided O:1

Conservation

PhyloP100: -0.948

Variant links:

Genes affected

FAM13A (HGNC:19367): (family with sequence similarity 13 member A) Predicted to enable GTPase activator activity. Predicted to be involved in regulation of small GTPase mediated signal transduction. Predicted to be located in cytosol. Implicated in chronic obstructive pulmonary disease. [provided by Alliance of Genome Resources, Apr 2022]

FAM13A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM13A	NM_014883.4 link	c.605+25827G>A		intron_variant	Intron 4 of 23	ENST00000264344.10	NP_055698.2	O94988-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM13A	ENST00000264344.10 link	c.605+25827G>A		intron_variant	Intron 4 of 23	5	NM_014883.4	ENSP00000264344.5		O94988-4

Frequencies

GnomAD3 genomes

AF:

0.575

AC:

87246

AN:

151864

Hom.:

25227

Cov.:

show subpopulations

Gnomad AFR

AF:

0.645

Gnomad AMI

AF:

0.491

Gnomad AMR

AF:

0.532

Gnomad ASJ

AF:

0.466

Gnomad EAS

AF:

0.560

Gnomad SAS

AF:

0.681

Gnomad FIN

AF:

0.580

Gnomad MID

AF:

0.395

Gnomad NFE

AF:

0.543

Gnomad OTH

AF:

0.527

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

GnomAD4 genome

AF:

0.574

AC:

87300

AN:

151982

Hom.:

25243

Cov.:

AF XY:

0.576

AC XY:

42778

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.644

Gnomad4 AMR

AF:

0.532

Gnomad4 ASJ

AF:

0.466

Gnomad4 EAS

AF:

0.560

Gnomad4 SAS

AF:

0.680

Gnomad4 FIN

AF:

0.580

Gnomad4 NFE

AF:

0.543

Gnomad4 OTH

AF:

0.532

Alfa

AF:

0.534

Hom.:

43797

Bravo

AF:

0.569

Asia WGS

AF:

0.620

AC:

2156

AN:

3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Chronic obstructive pulmonary disease

Other:1

Feb 03, 2020

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Significance: association

Review Status: no assertion criteria provided

Collection Method: case-control

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.092

DANN

Benign

0.24

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over