chr7-48226598-T-C

Variant names:

• chr7-48226598-T-C
• rs17712049
• NM_152701.5:c.469-664T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152701.5(ABCA13):​c.469-664T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.87 in 152,232 control chromosomes in the GnomAD database, including 57,823 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 0.87 (57823 hom., cov: 32)
• Consequence: ABCA13 NM_152701.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.47
• Publications: 4 publications found

Genes affected

ABCA13 (HGNC:14638): (ATP binding cassette subfamily A member 13) In human, the ATP-binding cassette (ABC) family of transmembrane transporters has at least 48 genes and 7 gene subfamilies. This gene is a member of ABC gene subfamily A (ABCA). Genes within the ABCA family typically encode several thousand amino acids. Like other ABC transmembrane transporter proteins, this protein has 12 or more transmembrane alpha-helix domains that likely arrange to form a single central chamber with multiple substrate binding sites. It is also predicted to have two large extracellular domains and two nucleotide binding domains as is typical for ABCA proteins. Alternative splice variants have been described but their biological validity has not been demonstrated.[provided by RefSeq, Mar 2009]

ABCA13 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCA13	NM_152701.5	c.469-664T>C		intron_variant	Intron 5 of 61	ENST00000435803.6	NP_689914.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCA13	ENST00000435803.6	c.469-664T>C		intron_variant	Intron 5 of 61	1	NM_152701.5	ENSP00000411096.1
ABCA13	ENST00000417403.5	n.469-664T>C		intron_variant	Intron 5 of 17	2		ENSP00000409268.1

Frequencies

GnomAD3 genomes AF: 0.870 AC: 132388 AN: 152114 Hom.: 57778 Cov.: 32

Gnomad AFR AF: 0.867

Gnomad AMI AF: 0.968

Gnomad AMR AF: 0.783

Gnomad ASJ AF: 0.894

Gnomad EAS AF: 0.795

Gnomad SAS AF: 0.813

Gnomad FIN AF: 0.891

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.896

Gnomad OTH AF: 0.871

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.870 AC: 132489 AN: 152232 Hom.: 57823 Cov.: 32 AF XY: 0.867 AC XY: 64537 AN XY: 74428

African (AFR) AF: 0.867 AC: 36010 AN: 41528

American (AMR) AF: 0.783 AC: 11975 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.894 AC: 3102 AN: 3470

East Asian (EAS) AF: 0.795 AC: 4103 AN: 5164

South Asian (SAS) AF: 0.814 AC: 3917 AN: 4814

European-Finnish (FIN) AF: 0.891 AC: 9460 AN: 10612

Middle Eastern (MID) AF: 0.861 AC: 253 AN: 294

European-Non Finnish (NFE) AF: 0.896 AC: 60945 AN: 68030

Other (OTH) AF: 0.871 AC: 1841 AN: 2114

Alfa AF: 0.886 Hom.: 246741

Bravo AF: 0.862

Asia WGS AF: 0.844 AC: 2935 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.11
DANN	Benign	0.44
PhyloP100		-4.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs17712049; hg19: chr7-48266195; COSMIC: COSV70041213;