rs3764650

Positions:

• chr19-1046521-T-G

Variant summary

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

The NM_019112.4(ABCA7):​c.1622+115T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 1,381,032 control chromosomes in the GnomAD database, including 11,058 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 0.15 (2175 hom., cov: 33)
  • Exomes 𝑓: 0.10 (8883 hom.)
• Consequence: ABCA7 NM_019112.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.893

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA7	NM_019112.4	c.1622+115T>G		intron_variant		ENST00000263094.11	NP_061985.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA7	ENST00000263094.11	c.1622+115T>G		intron_variant		5	NM_019112.4	ENSP00000263094	P1
ABCA7	ENST00000433129.6	n.2302+115T>G		intron_variant, non_coding_transcript_variant		1
ABCA7	ENST00000533574.1	n.263+117T>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22044 AN: 151930 Hom.: 2154 Cov.: 33

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.0926

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0311

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0900

Gnomad OTH AF: 0.152

GnomAD4 exome AF: 0.104 AC: 127913 AN: 1228986 Hom.: 8883 AF XY: 0.104 AC XY: 62942 AN XY: 606904

Gnomad4 AFR exome AF: 0.266

Gnomad4 AMR exome AF: 0.0695

Gnomad4 ASJ exome AF: 0.144

Gnomad4 EAS exome AF: 0.366

Gnomad4 SAS exome AF: 0.118

Gnomad4 FIN exome AF: 0.0369

Gnomad4 NFE exome AF: 0.0897

Gnomad4 OTH exome AF: 0.121

GnomAD4 genome AF: 0.145 AC: 22103 AN: 152046 Hom.: 2175 Cov.: 33 AF XY: 0.143 AC XY: 10607 AN XY: 74320

Gnomad4 AFR AF: 0.262

Gnomad4 AMR AF: 0.0925

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.320

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.0311

Gnomad4 NFE AF: 0.0900

Gnomad4 OTH AF: 0.161

Alfa AF: 0.103 Hom.: 1737

Bravo AF: 0.154

Asia WGS AF: 0.242 AC: 841 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.89
DANN	Benign	0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3764650; hg19: chr19-1046520; COSMIC: COSV54028967; COSMIC: COSV54028967;