NM_152701.5:c.12566-8684T>C

Variant names:

• chr7-48446353-T-C
• rs6966461
• NM_152701.5:c.12566-8684T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_152701.5(ABCA13):​c.12566-8684T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00894 in 150,858 control chromosomes in the GnomAD database, including 9 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 0.0089 (9 hom., cov: 31)
• Consequence: ABCA13 NM_152701.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• Publications: 1 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=-0.95).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00894 (1348/150858) while in subpopulation AFR AF = 0.031 (1273/41072). AF 95% confidence interval is 0.0296. There are 9 homozygotes in GnomAd4. There are 641 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152701.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA13	NM_152701.5	MANE Select	c.12566-8684T>C		intron	N/A	NP_689914.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA13	ENST00000435803.6	TSL:1 MANE Select	c.12566-8684T>C		intron	N/A	ENSP00000411096.1
	ABCA13	ENST00000544596.5	TSL:1	c.4484-8684T>C		intron	N/A	ENSP00000442634.2
	ABCA13	ENST00000611776.4	TSL:1	n.4485-8684T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00892 AC: 1345 AN: 150740 Hom.: 9 Cov.: 31

Gnomad AFR AF: 0.0310

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00389

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000737

Gnomad OTH AF: 0.00532

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

GnomAD4 genome AF: 0.00894 AC: 1348 AN: 150858 Hom.: 9 Cov.: 31 AF XY: 0.00872 AC XY: 641 AN XY: 73546

African (AFR) AF: 0.0310 AC: 1273 AN: 41072

American (AMR) AF: 0.00389 AC: 59 AN: 15168

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5086

South Asian (SAS) AF: 0.00 AC: 0 AN: 4756

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10174

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000737 AC: 5 AN: 67846

Other (OTH) AF: 0.00527 AC: 11 AN: 2088

Alfa AF: 0.00744 Hom.: 2

Bravo AF: 0.0102

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.38
DANN	Benign	0.64
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs6966461; hg19: chr7-48485950;