19-1043153-G-C

Variant names:

• chr19-1043153-G-C
• rs150820818
• NM_019112.4:c.692G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_019112.4(ABCA7):​c.692G>C​(p.Ser231Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,459,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ABCA7 NM_019112.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.64

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14840129).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA7	NM_019112.4	c.692G>C	p.Ser231Thr	missense_variant	Exon 8 of 47	ENST00000263094.11	NP_061985.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA7	ENST00000263094.11	c.692G>C	p.Ser231Thr	missense_variant	Exon 8 of 47	5	NM_019112.4	ENSP00000263094.6
ABCA7	ENST00000433129.6	n.1372G>C		non_coding_transcript_exon_variant	Exon 7 of 44	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000801 AC: 2 AN: 249560 Hom.: 0 AF XY: 0.0000148 AC XY: 2 AN XY: 135464

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459736 Hom.: 0 Cov.: 33 AF XY: 0.00000276 AC XY: 2 AN XY: 725908

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000448

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.24	T;T;.
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.40	T;.;T
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	1.1	L;L;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.7	N;N;.
REVEL	Benign	0.14
Sift	Uncertain	0.0050	D;D;.
Sift4G	Benign	0.12	T;T;D
Polyphen		0.35	B;B;B
Vest4		0.20
MutPred		0.16		Loss of phosphorylation at S231 (P = 0.0681);Loss of phosphorylation at S231 (P = 0.0681);.;
MVP		0.76
MPC		0.14
ClinPred		0.12	T
GERP RS		3.6
Varity_R		0.15
gMVP		0.39

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

Publications

LitVar

Other links and lift over

dbSNP: rs150820818; hg19: chr19-1043152;