4-88965146-C-T

Variant names:

• chr4-88965146-C-T
• rs1903003
• NM_014883.4:c.605+25827G>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.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
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -0.948
• Publications: 26 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 (SAS) allele frequency at 95% confidence interval = 0.66 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.605+25827G>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.605+25827G>A		intron	N/A	ENSP00000264344.5	O94988-4
	FAM13A	ENST00000511976.5	TSL:1	c.-22-26905G>A		intron	N/A	ENSP00000421914.1	E9PGM7
	FAM13A	ENST00000509094.5	TSL:1	c.605+25827G>A		intron	N/A	ENSP00000426517.1	D6RFM4

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87246 AN: 151864 Hom.: 25227 Cov.: 31

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.: 31 AF XY: 0.576 AC XY: 42778 AN XY: 74254

African (AFR) AF: 0.644 AC: 26689 AN: 41430

American (AMR) AF: 0.532 AC: 8133 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.466 AC: 1615 AN: 3468

East Asian (EAS) AF: 0.560 AC: 2890 AN: 5164

South Asian (SAS) AF: 0.680 AC: 3269 AN: 4810

European-Finnish (FIN) AF: 0.580 AC: 6118 AN: 10540

Middle Eastern (MID) AF: 0.404 AC: 118 AN: 292

European-Non Finnish (NFE) AF: 0.543 AC: 36901 AN: 67982

Other (OTH) AF: 0.532 AC: 1122 AN: 2108

Alfa AF: 0.543 Hom.: 92180

Bravo AF: 0.569

Asia WGS AF: 0.620 AC: 2156 AN: 3478

ClinVar

ClinVar submissions

Significance: association

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Chronic obstructive pulmonary disease (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.092
DANN	Benign	0.24
PhyloP100		-0.95
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: rs1903003; hg19: chr4-89886297; COSMIC: COSV107262855;