19-1041165-C-T

Position:

• chr19-1041165-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.-137-60C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0494 in 629,336 control chromosomes in the GnomAD database, including 1,146 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 0.065 (482 hom., cov: 32)
  • Exomes 𝑓: 0.044 (664 hom.)
• Consequence: ABCA7 NM_019112.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.644

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCA7	NM_019112.4	c.-137-60C>T		intron_variant		ENST00000263094.11	NP_061985.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCA7	ENST00000263094.11	c.-137-60C>T		intron_variant		5	NM_019112.4	ENSP00000263094.6

Frequencies

GnomAD3 genomes AF: 0.0650 AC: 9885 AN: 152012 Hom.: 477 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0328

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.0896

Gnomad SAS AF: 0.0640

Gnomad FIN AF: 0.0298

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0395

Gnomad OTH AF: 0.0551

GnomAD4 exome AF: 0.0444 AC: 21187 AN: 477206 Hom.: 664 Cov.: 5 AF XY: 0.0448 AC XY: 11287 AN XY: 252084

Gnomad4 AFR exome AF: 0.131

Gnomad4 AMR exome AF: 0.0238

Gnomad4 ASJ exome AF: 0.0276

Gnomad4 EAS exome AF: 0.0715

Gnomad4 SAS exome AF: 0.0613

Gnomad4 FIN exome AF: 0.0275

Gnomad4 NFE exome AF: 0.0389

Gnomad4 OTH exome AF: 0.0453

GnomAD4 genome AF: 0.0652 AC: 9915 AN: 152130 Hom.: 482 Cov.: 32 AF XY: 0.0648 AC XY: 4822 AN XY: 74364

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.0327

Gnomad4 ASJ AF: 0.0285

Gnomad4 EAS AF: 0.0896

Gnomad4 SAS AF: 0.0638

Gnomad4 FIN AF: 0.0298

Gnomad4 NFE AF: 0.0395

Gnomad4 OTH AF: 0.0560

Alfa AF: 0.0480 Hom.: 217

Bravo AF: 0.0681

Asia WGS AF: 0.0850 AC: 293 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.4
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3752228; hg19: chr19-1041164; COSMIC: COSV54036836; COSMIC: COSV54036836;