chr19-1041353-A-G

Variant names:

• chr19-1041353-A-G
• rs3752229
• NM_019112.4:c.-9A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 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 (no stars).

• 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 no assertion criteria provided B:1
• Conservation: PhyloP100: 0.0150
• Publications: 26 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 -13 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 VariationId is 3060463.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019112.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA7	NM_019112.4	MANE Select	c.-9A>G		5_prime_UTR	Exon 2 of 47	NP_061985.2	Q8IZY2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA7	ENST00000263094.11	TSL:5 MANE Select	c.-9A>G		5_prime_UTR	Exon 2 of 47	ENSP00000263094.6	Q8IZY2-1
	ABCA7	ENST00000433129.6	TSL:1	n.329A>G		non_coding_transcript_exon	Exon 2 of 44
	ABCA7	ENST00000525238.2	TSL:1	n.208A>G		non_coding_transcript_exon	Exon 2 of 4

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

GnomAD2 exomes AF: 0.0700 AC: 17579 AN: 251238 AF XY: 0.0715

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 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

African (AFR) AF: 0.00774 AC: 259 AN: 33480

American (AMR) AF: 0.0237 AC: 1061 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0522 AC: 1363 AN: 26134

East Asian (EAS) AF: 0.374 AC: 14839 AN: 39700

South Asian (SAS) AF: 0.105 AC: 9041 AN: 86254

European-Finnish (FIN) AF: 0.0260 AC: 1386 AN: 53246

Middle Eastern (MID) AF: 0.0494 AC: 285 AN: 5768

European-Non Finnish (NFE) AF: 0.0482 AC: 53571 AN: 1111894

Other (OTH) AF: 0.0646 AC: 3901 AN: 60390

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

African (AFR) AF: 0.0101 AC: 421 AN: 41538

American (AMR) AF: 0.0442 AC: 675 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0487 AC: 169 AN: 3468

East Asian (EAS) AF: 0.343 AC: 1774 AN: 5168

South Asian (SAS) AF: 0.126 AC: 606 AN: 4820

European-Finnish (FIN) AF: 0.0282 AC: 300 AN: 10622

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0461 AC: 3134 AN: 68010

Other (OTH) AF: 0.0653 AC: 138 AN: 2114

Alfa AF: 0.0440 Hom.: 391

Bravo AF: 0.0472

Asia WGS AF: 0.226 AC: 785 AN: 3478

EpiCase AF: 0.0456

EpiControl AF: 0.0477

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	ABCA7-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	12
DANN	Benign	0.64
PhyloP100		0.015
PromoterAI		0.015	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

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