rs2609255

Variant names:

• chr4-88890044-G-T
• rs2609255
• NM_014883.4:c.843+16335C>A

Variant summary

Our verdict is Benign. The variant received -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:2 O:2
• Conservation: PhyloP100: 0.0840
• Publications: 55 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014883.4. 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
	FAM13A	NM_014883.4	MANE Select	c.843+16335C>A		intron	N/A	NP_055698.2	O94988-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM13A	ENST00000264344.10	TSL:5 MANE Select	c.843+16335C>A		intron	N/A	ENSP00000264344.5	O94988-4
	FAM13A	ENST00000511976.5	TSL:1	c.216+16335C>A		intron	N/A	ENSP00000421914.1	E9PGM7
	FAM13A	ENST00000933309.1		c.843+16335C>A		intron	N/A	ENSP00000603368.1

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

African (AFR) AF: 0.702 AC: 29088 AN: 41460

American (AMR) AF: 0.742 AC: 11346 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.762 AC: 2640 AN: 3466

East Asian (EAS) AF: 0.549 AC: 2838 AN: 5174

South Asian (SAS) AF: 0.541 AC: 2605 AN: 4814

European-Finnish (FIN) AF: 0.628 AC: 6611 AN: 10522

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.785 AC: 53361 AN: 67994

Other (OTH) AF: 0.739 AC: 1562 AN: 2114

Alfa AF: 0.761 Hom.: 138467

Bravo AF: 0.739

Asia WGS AF: 0.579 AC: 2014 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance; association

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Combined pulmonary fibrosis-emphysema syndrome (1)
-	1	-	Susceptibility to severe coronavirus disease (COVID-19) (1)
-	-	-	Chronic obstructive pulmonary disease (1)
-	-	-	Interstitial lung disease 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.1
DANN	Benign	0.47
PhyloP100		0.084
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2609255; hg19: chr4-89811195;