rs4147911

chr19-1047688-C-Gchr19-1047688-C-T

Variant summary

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

The NM_019112.4(ABCA7):c.2269+34C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0933 in 1,545,166 control chromosomes in the GnomAD database, including 8,985 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 0.076 (732 hom., cov: 33)
  • Exomes 𝑓: 0.095 (8253 hom.)
• Consequence: ABCA7 NM_019112.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.634

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCA7	NM_019112.4	c.2269+34C>G		intron_variant		ENST00000263094.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCA7	ENST00000263094.11	c.2269+34C>G		intron_variant		5	NM_019112.4	P1
ABCA7	ENST00000433129.6	n.2949+34C>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0760 AC: 11544 AN: 151844 Hom.: 724 Cov.: 33

Gnomad AFR AF: 0.0203

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.0708

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.0313

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0894

Gnomad OTH AF: 0.105

GnomAD3 exomes AF: 0.104 AC: 17104 AN: 164352 Hom.: 1374 AF XY: 0.105 AC XY: 9674 AN XY: 91800

Gnomad AFR exome AF: 0.0149

Gnomad AMR exome AF: 0.0494

Gnomad ASJ exome AF: 0.143

Gnomad EAS exome AF: 0.343

Gnomad SAS exome AF: 0.116

Gnomad FIN exome AF: 0.0337

Gnomad NFE exome AF: 0.0909

Gnomad OTH exome AF: 0.101

GnomAD4 exome AF: 0.0952 AC: 132641 AN: 1393206 Hom.: 8253 Cov.: 35 AF XY: 0.0959 AC XY: 65853 AN XY: 686682

Gnomad4 AFR exome AF: 0.0154

Gnomad4 AMR exome AF: 0.0514

Gnomad4 ASJ exome AF: 0.143

Gnomad4 EAS exome AF: 0.366

Gnomad4 SAS exome AF: 0.114

Gnomad4 FIN exome AF: 0.0356

Gnomad4 NFE exome AF: 0.0889

Gnomad4 OTH exome AF: 0.104

GnomAD4 genome AF: 0.0761 AC: 11559 AN: 151960 Hom.: 732 Cov.: 33 AF XY: 0.0750 AC XY: 5566 AN XY: 74254

Gnomad4 AFR AF: 0.0203

Gnomad4 AMR AF: 0.0707

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.318

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.0313

Gnomad4 NFE AF: 0.0893

Gnomad4 OTH AF: 0.114

Alfa AF: 0.0490 Hom.: 78

Bravo AF: 0.0761

Asia WGS AF: 0.223 AC: 774 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.0
Dann	Benign	0.67

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: rs4147911; hg19: chr19-1047687;