chr4-88948181-T-C

Variant names:

• chr4-88948181-T-C
• rs2869967
• NM_014883.4:c.606-9940A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014883.4(FAM13A):​c.606-9940A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 151,900 control chromosomes in the GnomAD database, including 18,661 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.48 (18661 hom., cov: 31)
• Consequence: FAM13A NM_014883.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.655
• 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]

LOC105377327 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.656 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.606-9940A>G		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.606-9940A>G		intron	N/A	ENSP00000264344.5	O94988-4
	FAM13A	ENST00000511976.5	TSL:1	c.-22-9940A>G		intron	N/A	ENSP00000421914.1	E9PGM7
	FAM13A	ENST00000509094.5	TSL:1	c.606-9940A>G		intron	N/A	ENSP00000426517.1	D6RFM4

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73287 AN: 151782 Hom.: 18618 Cov.: 31

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.438

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

GnomAD4 genome AF: 0.483 AC: 73382 AN: 151900 Hom.: 18661 Cov.: 31 AF XY: 0.481 AC XY: 35676 AN XY: 74226

African (AFR) AF: 0.662 AC: 27430 AN: 41430

American (AMR) AF: 0.463 AC: 7055 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1039 AN: 3468

East Asian (EAS) AF: 0.516 AC: 2650 AN: 5136

South Asian (SAS) AF: 0.356 AC: 1712 AN: 4810

European-Finnish (FIN) AF: 0.430 AC: 4540 AN: 10550

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.406 AC: 27608 AN: 67936

Other (OTH) AF: 0.445 AC: 940 AN: 2112

Alfa AF: 0.423 Hom.: 48649

Bravo AF: 0.493

Asia WGS AF: 0.456 AC: 1587 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.63
PhyloP100		-0.66
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: rs2869967; hg19: chr4-89869332; COSMIC: COSV107262852;