rs817126

Variant names:

• chr17-69268198-A-G
• rs817126
• NM_172232.4:c.3031-142T>C

Your query was ambiguous. Multiple possible variants found:

• chr17-69268198-A-G
• chr17-69268198-A-T

Variant summary

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

The NM_172232.4(ABCA5):​c.3031-142T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 525,316 control chromosomes in the GnomAD database, including 32,610 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 0.31 (8016 hom., cov: 31)
  • Exomes 𝑓: 0.35 (24594 hom.)
• Consequence: ABCA5 NM_172232.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.972
• Publications: 5 publications found

Genes affected

ABCA5 (HGNC:35): (ATP binding cassette subfamily A member 5) The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intracellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, and White). This encoded protein is a member of the ABC1 subfamily. Members of the ABC1 subfamily comprise the only major ABC subfamily found exclusively in multicellular eukaryotes. This gene is clustered among 4 other ABC1 family members on 17q24, but neither the substrate nor the function of this gene is known. Alternative splicing of this gene results in several transcript variants; however, not all variants have been fully described. [provided by RefSeq, Jul 2008]

ABCA5 Gene-Disease associations (from GenCC):

• gingival fibromatosis-hypertrichosis syndrome

  Inheritance: AD, AR Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, G2P, Ambry Genetics
• ventricular tachycardia, familial

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA5	NM_172232.4	c.3031-142T>C		intron_variant	Intron 22 of 38	ENST00000392676.8	NP_758424.1
ABCA5	NM_018672.5	c.3031-142T>C		intron_variant	Intron 21 of 37		NP_061142.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA5	ENST00000392676.8	c.3031-142T>C		intron_variant	Intron 22 of 38	1	NM_172232.4	ENSP00000376443.2

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47602 AN: 151808 Hom.: 8013 Cov.: 31

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.579

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.311

GnomAD4 exome AF: 0.349 AC: 130400 AN: 373390 Hom.: 24594 AF XY: 0.350 AC XY: 68842 AN XY: 196452

African (AFR) AF: 0.209 AC: 2161 AN: 10340

American (AMR) AF: 0.417 AC: 5493 AN: 13186

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 4284 AN: 11468

East Asian (EAS) AF: 0.622 AC: 16724 AN: 26890

South Asian (SAS) AF: 0.389 AC: 11067 AN: 28434

European-Finnish (FIN) AF: 0.368 AC: 13839 AN: 37580

Middle Eastern (MID) AF: 0.327 AC: 533 AN: 1632

European-Non Finnish (NFE) AF: 0.311 AC: 69231 AN: 222310

Other (OTH) AF: 0.328 AC: 7068 AN: 21550

GnomAD4 genome AF: 0.313 AC: 47626 AN: 151926 Hom.: 8016 Cov.: 31 AF XY: 0.319 AC XY: 23667 AN XY: 74220

African (AFR) AF: 0.214 AC: 8878 AN: 41450

American (AMR) AF: 0.382 AC: 5826 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 1315 AN: 3472

East Asian (EAS) AF: 0.579 AC: 2974 AN: 5138

South Asian (SAS) AF: 0.395 AC: 1905 AN: 4818

European-Finnish (FIN) AF: 0.379 AC: 4001 AN: 10554

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.318 AC: 21592 AN: 67944

Other (OTH) AF: 0.312 AC: 657 AN: 2108

Alfa AF: 0.319 Hom.: 13746

Bravo AF: 0.310

Asia WGS AF: 0.434 AC: 1506 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.29
DANN	Benign	0.66
PhyloP100		-0.97
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: rs817126; hg19: chr17-67264339;