NM_019112.4:c.1622+115T>C

Variant names:

• chr19-1046521-T-C
• rs3764650
• NM_019112.4:c.1622+115T>C

GermlineCancer (beta)

Variant summary

Our verdict is Likely benign.

-2 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -2 classification points (ACMG Germline Pathogenicity v2019). PM2BP4_Strong

The NM_019112.4(ABCA7):c.1622+115T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.000000813 (AC=1) in the gnomAD database across 1,229,648 control chromosomes (no homozygotes observed). The grpmax filtering allele frequency (95% CI) is 0.00000104. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.1e-7 (0 hom.)
• Consequence: ABCA7 NM_019112.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.893
• Publications: 0 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)

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Likely_benign. The variant received -2 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM2Absent/extremely low in population databases		Very rare in gnomAD for AR/unknown gene (popmax AF < threshold/10) — PM2; GnomAD popmax AF = 0.00000104 — very rare for unknown gene (threshold 0.001) — PM2 moderate.
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

Variant Effect in Transcripts

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

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	ABCA7 NM_019112.4	MANE Select	c.1622+115T>C	intron	Intron 13 of 46	Prot: NP_061985.2 UniProt:

ABCA7 NM_019112.4

MANE Select

HGVSc / HGVSpc.1622+115T>C

Exon rankIntron 13 of 46

intron

Prot: NP_061985.2UniProt: Q8IZY2-1

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	ABCA7 ENST00000263094.11	TSL:5MANE Select	c.1622+115T>C	intron	Intron 13 of 46	Prot: ENSP00000263094.6 UniProt:
	ABCA7 ENST00000433129.6	TSL:1	n.2302+115T>C	intron	Intron 12 of 43	Prot:
	ABCA7 ENST00000533574.1	TSL:4	n.263+117T>C	intron	Intron 2 of 3	Prot:

ABCA7 ENST00000263094.11

TSL:5MANE Select

HGVSc / HGVSpc.1622+115T>C

Exon rankIntron 13 of 46

intron

Prot: ENSP00000263094.6UniProt: Q8IZY2-1

ABCA7 ENST00000433129.6

TSL:1

HGVSc / HGVSpn.2302+115T>C

Exon rankIntron 12 of 43

intron

Prot:

ABCA7 ENST00000533574.1

TSL:4

HGVSc / HGVSpn.263+117T>C

Exon rankIntron 2 of 3

intron

Prot:

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 3 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:33
GnomAD4 exome	AF: 8.13e-7	AC:1	Hom:0	AN:1229648	Cov:
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:33

Showing 3 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	0.43
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.96
DANN	Benign	0.49
GPN-Star LLR	N/A	0.75
GPN-Star score	N/A	-0.75
PhyloP100	Benign	-0.89
RBP_binding_hub_radar	N/A	0.0
RBP_regulation_power_radar	N/A	1.1

Showing 9 of 9 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs3764650;

hg19: chr19-1046520;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar