rs658979

Positions:

• chr17-49218979-G-A

Variant summary

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

The NM_016428.3(ABI3):​c.463-561G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 151,674 control chromosomes in the GnomAD database, including 7,761 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 0.29 (7761 hom., cov: 30)
• Consequence: ABI3 NM_016428.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65

Genes affected

ABI3 (HGNC:29859): (ABI family member 3) This gene encodes a member of an adaptor protein family. Members of this family encode proteins containing a homeobox homology domain, proline rich region and Src-homology 3 (SH3) domain, and are components of the Abi/WAVE complex which regulates actin polymerization. The encoded protein inhibits ectopic metastasis of tumor cells as well as cell migration. This may be accomplished through interaction with p21-activated kinase. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABI3	NM_016428.3	c.463-561G>A		intron_variant		ENST00000225941.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABI3	ENST00000225941.6	c.463-561G>A		intron_variant		1	NM_016428.3	P3
ABI3	ENST00000419580.6	c.445-561G>A		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43506 AN: 151556 Hom.: 7728 Cov.: 30

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.258

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

GnomAD4 genome AF: 0.287 AC: 43602 AN: 151674 Hom.: 7761 Cov.: 30 AF XY: 0.292 AC XY: 21624 AN XY: 74130

Gnomad4 AFR AF: 0.497

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.243

Gnomad4 SAS AF: 0.331

Gnomad4 FIN AF: 0.232

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.259

Alfa AF: 0.204 Hom.: 3272

Bravo AF: 0.299

Asia WGS AF: 0.316 AC: 1095 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.87
DANN	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs658979; hg19: chr17-47296341;