chr17-69153832-G-A

Variant names:

• chr17-69153832-G-A
• rs10491178
• NM_001377321.1:c.3964C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001377321.1(ABCA10):​c.3964C>T​(p.Arg1322*) variant causes a stop gained, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0614 in 1,611,562 control chromosomes in the GnomAD database, including 3,739 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.073 (537 hom., cov: 32)
  • Exomes 𝑓: 0.060 (3202 hom.)
• Consequence: ABCA10 NM_001377321.1 stop_gained, splice_region
• Scores: Splicing: ADA: 0.004318
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02

Genes affected

ABCA10 (HGNC:30): (ATP binding cassette subfamily A member 10) 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. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA10	NM_001377321.1	c.3964C>T	p.Arg1322*	stop_gained, splice_region_variant	Exon 32 of 39	ENST00000690296.1	NP_001364250.1
ABCA10	NM_080282.4	c.3964C>T	p.Arg1322*	stop_gained, splice_region_variant	Exon 33 of 40		NP_525021.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA10	ENST00000690296.1	c.3964C>T	p.Arg1322*	stop_gained, splice_region_variant	Exon 32 of 39		NM_001377321.1	ENSP00000509702.1
ABCA10	ENST00000522406.5	n.*2892C>T		splice_region_variant, non_coding_transcript_exon_variant	Exon 34 of 41	1		ENSP00000429853.1
ABCA10	ENST00000522406.5	n.*2892C>T		3_prime_UTR_variant	Exon 34 of 41	1		ENSP00000429853.1

Frequencies

GnomAD3 genomes AF: 0.0729 AC: 11075 AN: 151950 Hom.: 537 Cov.: 32

Gnomad AFR AF: 0.0711

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.0647

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.0696

Gnomad FIN AF: 0.0790

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0523

Gnomad OTH AF: 0.0800

GnomAD2 exomes AF: 0.0811 AC: 20208 AN: 249050 AF XY: 0.0760

Gnomad AFR exome AF: 0.0743

Gnomad AMR exome AF: 0.167

Gnomad ASJ exome AF: 0.0653

Gnomad EAS exome AF: 0.139

Gnomad FIN exome AF: 0.0870

Gnomad NFE exome AF: 0.0507

Gnomad OTH exome AF: 0.0760

GnomAD4 exome AF: 0.0602 AC: 87900 AN: 1459494 Hom.: 3202 Cov.: 30 AF XY: 0.0597 AC XY: 43357 AN XY: 725910

Gnomad4 AFR exome AF: 0.0736 AC: 2460 AN: 33422

Gnomad4 AMR exome AF: 0.166 AC: 7343 AN: 44340

Gnomad4 ASJ exome AF: 0.0629 AC: 1638 AN: 26026

Gnomad4 EAS exome AF: 0.118 AC: 4686 AN: 39646

Gnomad4 SAS exome AF: 0.0697 AC: 5974 AN: 85692

Gnomad4 FIN exome AF: 0.0851 AC: 4538 AN: 53338

Gnomad4 NFE exome AF: 0.0512 AC: 56828 AN: 1110982

Gnomad4 Remaining exome AF: 0.0664 AC: 4006 AN: 60296

GnomAD4 genome AF: 0.0730 AC: 11095 AN: 152068 Hom.: 537 Cov.: 32 AF XY: 0.0768 AC XY: 5708 AN XY: 74324

Gnomad4 AFR AF: 0.0711 AC: 0.0711427 AN: 0.0711427

Gnomad4 AMR AF: 0.153 AC: 0.15301 AN: 0.15301

Gnomad4 ASJ AF: 0.0647 AC: 0.0647025 AN: 0.0647025

Gnomad4 EAS AF: 0.121 AC: 0.121423 AN: 0.121423

Gnomad4 SAS AF: 0.0690 AC: 0.0689942 AN: 0.0689942

Gnomad4 FIN AF: 0.0790 AC: 0.0790271 AN: 0.0790271

Gnomad4 NFE AF: 0.0524 AC: 0.0523683 AN: 0.0523683

Gnomad4 OTH AF: 0.0825 AC: 0.0824645 AN: 0.0824645

Alfa AF: 0.0603 Hom.: 1965

Bravo AF: 0.0789

TwinsUK AF: 0.0537 AC: 199

ALSPAC AF: 0.0485 AC: 187

ESP6500AA AF: 0.0738 AC: 325

ESP6500EA AF: 0.0530 AC: 456

ExAC AF: 0.0747 AC: 9064

Asia WGS AF: 0.0910 AC: 318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	33
DANN	Benign	0.87
Eigen	Benign	-0.88
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0092	N
Vest4		0.031
GERP RS		-7.5
Mutation Taster		=65/135	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0043
dbscSNV1_RF	Benign	0.48
SpliceAI score (max)		0.030		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: rs10491178; hg19: chr17-67149973; COSMIC: COSV52219689; COSMIC: COSV52219689;