17-49213433-T-G

Variant names:

• chr17-49213433-T-G
• rs627386
• NM_016428.3:c.117+2592T>G

Variant summary

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

The NM_016428.3(ABI3):​c.117+2592T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.965 in 152,194 control chromosomes in the GnomAD database, including 70,896 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 0.96 (70896 hom., cov: 30)
• Consequence: ABI3 NM_016428.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 7 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 (SAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016428.3. 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
	ABI3	NM_016428.3	MANE Select	c.117+2592T>G		intron	N/A	NP_057512.2	Q9P2A4-1
	ABI3	NM_001135186.2		c.117+2592T>G		intron	N/A	NP_001128658.2	Q9P2A4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABI3	ENST00000225941.6	TSL:1 MANE Select	c.117+2592T>G		intron	N/A	ENSP00000225941.1	Q9P2A4-1
	ABI3	ENST00000881782.1		c.117+2592T>G		intron	N/A	ENSP00000551841.1
	ABI3	ENST00000881777.1		c.117+2592T>G		intron	N/A	ENSP00000551836.1

Frequencies

GnomAD3 genomes AF: 0.965 AC: 146742 AN: 152076 Hom.: 70854 Cov.: 30

Gnomad AFR AF: 0.931

Gnomad AMI AF: 0.921

Gnomad AMR AF: 0.968

Gnomad ASJ AF: 0.970

Gnomad EAS AF: 0.989

Gnomad SAS AF: 0.991

Gnomad FIN AF: 0.993

Gnomad MID AF: 0.978

Gnomad NFE AF: 0.977

Gnomad OTH AF: 0.968

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

GnomAD4 genome AF: 0.965 AC: 146841 AN: 152194 Hom.: 70896 Cov.: 30 AF XY: 0.966 AC XY: 71880 AN XY: 74414

African (AFR) AF: 0.931 AC: 38635 AN: 41504

American (AMR) AF: 0.968 AC: 14803 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.970 AC: 3367 AN: 3472

East Asian (EAS) AF: 0.989 AC: 5116 AN: 5172

South Asian (SAS) AF: 0.991 AC: 4761 AN: 4804

European-Finnish (FIN) AF: 0.993 AC: 10540 AN: 10618

Middle Eastern (MID) AF: 0.980 AC: 288 AN: 294

European-Non Finnish (NFE) AF: 0.977 AC: 66450 AN: 68024

Other (OTH) AF: 0.968 AC: 2045 AN: 2112

Alfa AF: 0.964 Hom.: 42946

Bravo AF: 0.961

Asia WGS AF: 0.986 AC: 3428 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.57
DANN	Benign	0.34
PhyloP100		-1.0
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: rs627386; hg19: chr17-47290795;