rs4147914

Variant names:

• chr19-1049270-G-A
• rs4147914
• NM_019112.4:c.2385G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-1049270-G-A
• chr19-1049270-G-C
• chr19-1049270-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_019112.4(ABCA7):​c.2385G>A​(p.Leu795Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 1,602,504 control chromosomes in the GnomAD database, including 22,492 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2227 hom., cov: 30)
  • Exomes 𝑓: 0.16 (20265 hom.)
• Consequence: ABCA7 NM_019112.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.50
• Publications: 27 publications found

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]

ABCA7 Gene-Disease associations (from GenCC):

• Alzheimer disease 9

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 19-1049270-G-A is Benign according to our data. Variant chr19-1049270-G-A is described in ClinVar as Benign. ClinVar VariationId is 1257803.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.5 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA7	NM_019112.4	c.2385G>A	p.Leu795Leu	synonymous_variant	Exon 18 of 47	ENST00000263094.11	NP_061985.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA7	ENST00000263094.11	c.2385G>A	p.Leu795Leu	synonymous_variant	Exon 18 of 47	5	NM_019112.4	ENSP00000263094.6
ABCA7	ENST00000433129.6	n.3065G>A		non_coding_transcript_exon_variant	Exon 17 of 44	1
ABCA7	ENST00000435683.7	n.-145G>A		upstream_gene_variant		5		ENSP00000465322.2

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24373 AN: 151786 Hom.: 2217 Cov.: 30

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.181

GnomAD2 exomes AF: 0.174 AC: 42184 AN: 242114 AF XY: 0.178

Gnomad AFR exome AF: 0.169

Gnomad AMR exome AF: 0.107

Gnomad ASJ exome AF: 0.222

Gnomad EAS exome AF: 0.397

Gnomad FIN exome AF: 0.131

Gnomad NFE exome AF: 0.137

Gnomad OTH exome AF: 0.158

GnomAD4 exome AF: 0.156 AC: 226540 AN: 1450600 Hom.: 20265 Cov.: 34 AF XY: 0.159 AC XY: 114545 AN XY: 720502

African (AFR) AF: 0.164 AC: 5472 AN: 33310

American (AMR) AF: 0.111 AC: 4902 AN: 44118

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 5614 AN: 25524

East Asian (EAS) AF: 0.422 AC: 16687 AN: 39530

South Asian (SAS) AF: 0.264 AC: 22524 AN: 85320

European-Finnish (FIN) AF: 0.130 AC: 6760 AN: 51876

Middle Eastern (MID) AF: 0.174 AC: 995 AN: 5722

European-Non Finnish (NFE) AF: 0.138 AC: 153082 AN: 1105336

Other (OTH) AF: 0.175 AC: 10504 AN: 59864

GnomAD4 genome AF: 0.161 AC: 24404 AN: 151904 Hom.: 2227 Cov.: 30 AF XY: 0.162 AC XY: 12008 AN XY: 74242

African (AFR) AF: 0.166 AC: 6854 AN: 41382

American (AMR) AF: 0.128 AC: 1953 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 738 AN: 3470

East Asian (EAS) AF: 0.380 AC: 1955 AN: 5142

South Asian (SAS) AF: 0.290 AC: 1399 AN: 4818

European-Finnish (FIN) AF: 0.132 AC: 1402 AN: 10602

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.139 AC: 9449 AN: 67906

Other (OTH) AF: 0.189 AC: 398 AN: 2104

Alfa AF: 0.148 Hom.: 1239

Bravo AF: 0.157

Asia WGS AF: 0.343 AC: 1192 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 23, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 28171541) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	5.6
DANN	Benign	0.56
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs4147914; hg19: chr19-1049269; COSMIC: COSV54030523; COSMIC: COSV54030523;