rs2609255

chr4-88890044-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014883.4(FAM13A):c.843+16335C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 152,032 control chromosomes in the GnomAD database, including 40,901 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance,association (no stars).

• Frequency: Genomes: 𝑓 0.73 (40901 hom., cov: 31)
• Consequence: FAM13A NM_014883.4 intron
• Clinical Significance: Uncertain significance; association no assertion criteria provided U:1 O:2
• Conservation: PhyloP100: 0.0840

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM13A	NM_014883.4	c.843+16335C>A		intron_variant		ENST00000264344.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM13A	ENST00000264344.10	c.843+16335C>A		intron_variant		5	NM_014883.4	P1

Frequencies

GnomAD3 genomes AF: 0.730 AC: 110907 AN: 151914 Hom.: 40856 Cov.: 31

Gnomad AFR AF: 0.701

Gnomad AMI AF: 0.814

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.785

Gnomad OTH AF: 0.735

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

GnomAD4 genome AF: 0.730 AC: 111004 AN: 152032 Hom.: 40901 Cov.: 31 AF XY: 0.719 AC XY: 53403 AN XY: 74288

Gnomad4 AFR AF: 0.702

Gnomad4 AMR AF: 0.742

Gnomad4 ASJ AF: 0.762

Gnomad4 EAS AF: 0.549

Gnomad4 SAS AF: 0.541

Gnomad4 FIN AF: 0.628

Gnomad4 NFE AF: 0.785

Gnomad4 OTH AF: 0.739

Alfa AF: 0.765 Hom.: 57584

Bravo AF: 0.739

Asia WGS AF: 0.579 AC: 2014 AN: 3478

ClinVar

Significance: Uncertain significance; association

Submissions summary: Uncertain:1 Other:2

Revision: no assertion criteria provided

Submissions by phenotype

Combined pulmonary fibrosis-emphysema syndrome Uncertain:1

Uncertain significance, no assertion criteria provided

case-control

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

May 04, 2021

- -

Interstitial lung disease 2 Other:1

association, no assertion criteria provided

case-control

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

May 04, 2021

- -

Chronic obstructive pulmonary disease Other:1

association, no assertion criteria provided

case-control

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

May 04, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	1.1
Dann	Benign	0.47

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

Other links and lift over

dbSNP: rs2609255; hg19: chr4-89811195;