chr17-49218979-G-A

Variant names:

• chr17-49218979-G-A
• rs658979
• NM_016428.3:c.463-561G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ABI3	NM_016428.3	c.463-561G>A		intron_variant	Intron 3 of 7	ENST00000225941.6	NP_057512.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABI3	ENST00000225941.6	c.463-561G>A		intron_variant	Intron 3 of 7	1	NM_016428.3	ENSP00000225941.1
ABI3	ENST00000419580.6	c.445-561G>A		intron_variant	Intron 3 of 7	5		ENSP00000406651.2

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

African (AFR) AF: 0.497 AC: 20492 AN: 41256

American (AMR) AF: 0.309 AC: 4701 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 757 AN: 3464

East Asian (EAS) AF: 0.243 AC: 1251 AN: 5152

South Asian (SAS) AF: 0.331 AC: 1592 AN: 4812

European-Finnish (FIN) AF: 0.232 AC: 2446 AN: 10540

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11651 AN: 67902

Other (OTH) AF: 0.259 AC: 546 AN: 2110

Alfa AF: 0.205 Hom.: 3792

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
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs658979; hg19: chr17-47296341;