19-1041353-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_019112.4(ABCA7):c.-9A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0577 in 1,613,820 control chromosomes in the GnomAD database, including 5,453 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.048 (503 hom., cov: 32)
  • Exomes 𝑓: 0.059 (4950 hom.)
• Consequence: ABCA7 NM_019112.4 5_prime_UTR
• Scores: Splicing: ADA: 0.00002728
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0150

Genes affected

ABCA7 (HGNC:37): (ATP binding cassette subfamily A member 7) The 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 intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This 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 full transporter has been detected predominantly in myelo-lymphatic tissues with the highest expression in peripheral leukocytes, thymus, spleen, and bone marrow. The function of this protein is not yet known; however, the expression pattern suggests a role in lipid homeostasis in cells of the immune system. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 19-1041353-A-G is Benign according to our data. Variant chr19-1041353-A-G is described in ClinVar as [Benign]. Clinvar id is 3060463.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCA7	NM_019112.4	c.-9A>G		5_prime_UTR_variant	2/47	ENST00000263094.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCA7	ENST00000263094.11	c.-9A>G		5_prime_UTR_variant	2/47	5	NM_019112.4	P1

Frequencies

GnomAD3 genomes AF: 0.0482 AC: 7333 AN: 152116 Hom.: 493 Cov.: 32

Gnomad AFR AF: 0.0102

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.0441

Gnomad ASJ AF: 0.0487

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.0282

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0461

Gnomad OTH AF: 0.0559

GnomAD3 exomes AF: 0.0700 AC: 17579 AN: 251238 Hom.: 1595 AF XY: 0.0715 AC XY: 9716 AN XY: 135806

Gnomad AFR exome AF: 0.00904

Gnomad AMR exome AF: 0.0224

Gnomad ASJ exome AF: 0.0540

Gnomad EAS exome AF: 0.369

Gnomad SAS exome AF: 0.107

Gnomad FIN exome AF: 0.0238

Gnomad NFE exome AF: 0.0456

Gnomad OTH exome AF: 0.0564

GnomAD4 exome AF: 0.0586 AC: 85706 AN: 1461586 Hom.: 4950 Cov.: 32 AF XY: 0.0598 AC XY: 43506 AN XY: 727074

Gnomad4 AFR exome AF: 0.00774

Gnomad4 AMR exome AF: 0.0237

Gnomad4 ASJ exome AF: 0.0522

Gnomad4 EAS exome AF: 0.374

Gnomad4 SAS exome AF: 0.105

Gnomad4 FIN exome AF: 0.0260

Gnomad4 NFE exome AF: 0.0482

Gnomad4 OTH exome AF: 0.0646

GnomAD4 genome AF: 0.0483 AC: 7354 AN: 152234 Hom.: 503 Cov.: 32 AF XY: 0.0507 AC XY: 3771 AN XY: 74432

Gnomad4 AFR AF: 0.0101

Gnomad4 AMR AF: 0.0442

Gnomad4 ASJ AF: 0.0487

Gnomad4 EAS AF: 0.343

Gnomad4 SAS AF: 0.126

Gnomad4 FIN AF: 0.0282

Gnomad4 NFE AF: 0.0461

Gnomad4 OTH AF: 0.0653

Alfa AF: 0.0463 Hom.: 322

Bravo AF: 0.0472

Asia WGS AF: 0.226 AC: 785 AN: 3478

EpiCase AF: 0.0456

EpiControl AF: 0.0477

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

ABCA7-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 29, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	12
Dann	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000027
dbscSNV1_RF	Benign	0.0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3752229; hg19: chr19-1041352; COSMIC: COSV54023994; COSMIC: COSV54023994;