chr4-88995984-A-G

Variant names:

• chr4-88995984-A-G
• rs10007590
• NM_014883.4:c.428-4834T>C

Variant summary

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

The NM_014883.4(FAM13A):​c.428-4834T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,212 control chromosomes in the GnomAD database, including 2,321 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 0.17 (2321 hom., cov: 33)
• Consequence: FAM13A NM_014883.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.49
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM13A	NM_014883.4	c.428-4834T>C		intron_variant	Intron 3 of 23	ENST00000264344.10	NP_055698.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM13A	ENST00000264344.10	c.428-4834T>C		intron_variant	Intron 3 of 23	5	NM_014883.4	ENSP00000264344.5

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26136 AN: 152094 Hom.: 2321 Cov.: 33

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.0671

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.168

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

GnomAD4 genome AF: 0.172 AC: 26151 AN: 152212 Hom.: 2321 Cov.: 33 AF XY: 0.173 AC XY: 12895 AN XY: 74400

African (AFR) AF: 0.167 AC: 6927 AN: 41538

American (AMR) AF: 0.150 AC: 2294 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 702 AN: 3470

East Asian (EAS) AF: 0.0668 AC: 346 AN: 5176

South Asian (SAS) AF: 0.268 AC: 1291 AN: 4816

European-Finnish (FIN) AF: 0.184 AC: 1945 AN: 10592

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12112 AN: 68006

Other (OTH) AF: 0.166 AC: 351 AN: 2114

Alfa AF: 0.174 Hom.: 7493

Bravo AF: 0.168

Asia WGS AF: 0.176 AC: 610 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.98
DANN	Benign	0.82
PhyloP100		-2.5
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: rs10007590; hg19: chr4-89917135;