19-1051215-A-G

Variant names:

• chr19-1051215-A-G
• rs3752240
• NM_019112.4:c.2745A>G

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.2745A>G​(p.Val915Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 1,610,496 control chromosomes in the GnomAD database, including 98,250 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (9288 hom., cov: 32)
  • Exomes 𝑓: 0.34 (88962 hom.)
• Consequence: ABCA7 NM_019112.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -6.55
• Publications: 41 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=-0.92).
• BP6: Variant 19-1051215-A-G is Benign according to our data. Variant chr19-1051215-A-G is described in ClinVar as Benign. ClinVar VariationId is 1241058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-6.55 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA7	NM_019112.4	c.2745A>G	p.Val915Val	synonymous_variant	Exon 20 of 47	ENST00000263094.11	NP_061985.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA7	ENST00000263094.11	c.2745A>G	p.Val915Val	synonymous_variant	Exon 20 of 47	5	NM_019112.4	ENSP00000263094.6
ABCA7	ENST00000433129.6	n.3425A>G		non_coding_transcript_exon_variant	Exon 19 of 44	1
ABCA7	ENST00000435683.7	n.216A>G		non_coding_transcript_exon_variant	Exon 3 of 29	5		ENSP00000465322.2

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52467 AN: 151884 Hom.: 9276 Cov.: 32

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.301

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.338

GnomAD2 exomes AF: 0.337 AC: 83406 AN: 247622 AF XY: 0.332

Gnomad AFR exome AF: 0.366

Gnomad AMR exome AF: 0.399

Gnomad ASJ exome AF: 0.398

Gnomad EAS exome AF: 0.125

Gnomad FIN exome AF: 0.357

Gnomad NFE exome AF: 0.360

Gnomad OTH exome AF: 0.347

GnomAD4 exome AF: 0.344 AC: 502146 AN: 1458494 Hom.: 88962 Cov.: 62 AF XY: 0.342 AC XY: 248476 AN XY: 725546

African (AFR) AF: 0.366 AC: 12246 AN: 33478

American (AMR) AF: 0.393 AC: 17538 AN: 44638

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 10486 AN: 26124

East Asian (EAS) AF: 0.106 AC: 4217 AN: 39684

South Asian (SAS) AF: 0.262 AC: 22576 AN: 86234

European-Finnish (FIN) AF: 0.357 AC: 18040 AN: 50550

Middle Eastern (MID) AF: 0.417 AC: 2400 AN: 5750

European-Non Finnish (NFE) AF: 0.355 AC: 394585 AN: 1111698

Other (OTH) AF: 0.332 AC: 20058 AN: 60338

GnomAD4 genome AF: 0.345 AC: 52506 AN: 152002 Hom.: 9288 Cov.: 32 AF XY: 0.341 AC XY: 25322 AN XY: 74284

African (AFR) AF: 0.366 AC: 15163 AN: 41468

American (AMR) AF: 0.369 AC: 5632 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1421 AN: 3472

East Asian (EAS) AF: 0.121 AC: 628 AN: 5186

South Asian (SAS) AF: 0.244 AC: 1175 AN: 4814

European-Finnish (FIN) AF: 0.338 AC: 3567 AN: 10552

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.351 AC: 23830 AN: 67948

Other (OTH) AF: 0.334 AC: 705 AN: 2110

Alfa AF: 0.352 Hom.: 35990

Bravo AF: 0.352

Asia WGS AF: 0.197 AC: 687 AN: 3478

EpiCase AF: 0.354

EpiControl AF: 0.364

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

- -

Sep 21, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.015
DANN	Benign	0.44
PhyloP100		-6.6
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3752240; hg19: chr19-1051214; COSMIC: COSV54028986; COSMIC: COSV54028986;