17-69262092-G-A

Position:

• chr17-69262092-G-A

Variant summary

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

The NM_172232.4(ABCA5):​c.3316-344C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0893 in 152,032 control chromosomes in the GnomAD database, including 646 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 0.089 (646 hom., cov: 32)
• Consequence: ABCA5 NM_172232.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0630

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCA5	NM_172232.4	c.3316-344C>T		intron_variant		ENST00000392676.8
ABCA5	NM_018672.5	c.3316-344C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCA5	ENST00000392676.8	c.3316-344C>T		intron_variant		1	NM_172232.4	P1

Frequencies

GnomAD3 genomes AF: 0.0893 AC: 13566 AN: 151914 Hom.: 643 Cov.: 32

Gnomad AFR AF: 0.0903

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.0603

Gnomad ASJ AF: 0.0727

Gnomad EAS AF: 0.0623

Gnomad SAS AF: 0.0784

Gnomad FIN AF: 0.0982

Gnomad MID AF: 0.0796

Gnomad NFE AF: 0.0968

Gnomad OTH AF: 0.0704

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

GnomAD4 genome AF: 0.0893 AC: 13577 AN: 152032 Hom.: 646 Cov.: 32 AF XY: 0.0875 AC XY: 6503 AN XY: 74290

Gnomad4 AFR AF: 0.0905

Gnomad4 AMR AF: 0.0601

Gnomad4 ASJ AF: 0.0727

Gnomad4 EAS AF: 0.0620

Gnomad4 SAS AF: 0.0779

Gnomad4 FIN AF: 0.0982

Gnomad4 NFE AF: 0.0968

Gnomad4 OTH AF: 0.0697

Alfa AF: 0.0940 Hom.: 325

Bravo AF: 0.0867

Asia WGS AF: 0.0540 AC: 188 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs9895649; hg19: chr17-67258233;