rs9895649

Variant names:

• chr17-69262092-G-A
• rs9895649
• NM_172232.4:c.3316-344C>T

Variant summary

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

The NM_172232.4(ABCA5):​c.3316-344C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0893 in 152,032 control chromosomes in the GnomAD database, including 646 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 0.089 (646 hom., cov: 32)
• Consequence: ABCA5 NM_172232.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0630
• Publications: 4 publications found

Genes affected

ABCA5 (HGNC:35): (ATP binding cassette subfamily A member 5) The membrane-associated 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 intracellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, and White). This encoded 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 gene is clustered among 4 other ABC1 family members on 17q24, but neither the substrate nor the function of this gene is known. Alternative splicing of this gene results in several transcript variants; however, not all variants have been fully described. [provided by RefSeq, Jul 2008]

ABCA5 Gene-Disease associations (from GenCC):

• gingival fibromatosis-hypertrichosis syndrome

  Inheritance: AR, AD Classification: SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, G2P, Orphanet
• ventricular tachycardia, familial

  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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0948 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172232.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA5	NM_172232.4	MANE Select	c.3316-344C>T		intron	N/A	NP_758424.1	Q8WWZ7-1
	ABCA5	NM_018672.5		c.3316-344C>T		intron	N/A	NP_061142.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCA5	ENST00000392676.8	TSL:1 MANE Select	c.3316-344C>T		intron	N/A	ENSP00000376443.2	Q8WWZ7-1
	ABCA5	ENST00000588877.5	TSL:1	c.3316-344C>T		intron	N/A	ENSP00000467882.1	Q8WWZ7-1
	ABCA5	ENST00000586995.5	TSL:1	n.*1082-344C>T		intron	N/A	ENSP00000467251.1	Q6N017

Frequencies

GnomAD3 genomes AF: 0.0893 AC: 13566 AN: 151914 Hom.: 643 Cov.: 32

Gnomad AFR AF: 0.0903

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.0603

Gnomad ASJ AF: 0.0727

Gnomad EAS AF: 0.0623

Gnomad SAS AF: 0.0784

Gnomad FIN AF: 0.0982

Gnomad MID AF: 0.0796

Gnomad NFE AF: 0.0968

Gnomad OTH AF: 0.0704

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

GnomAD4 genome AF: 0.0893 AC: 13577 AN: 152032 Hom.: 646 Cov.: 32 AF XY: 0.0875 AC XY: 6503 AN XY: 74290

African (AFR) AF: 0.0905 AC: 3750 AN: 41454

American (AMR) AF: 0.0601 AC: 918 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0727 AC: 252 AN: 3468

East Asian (EAS) AF: 0.0620 AC: 321 AN: 5174

South Asian (SAS) AF: 0.0779 AC: 375 AN: 4816

European-Finnish (FIN) AF: 0.0982 AC: 1037 AN: 10556

Middle Eastern (MID) AF: 0.0822 AC: 24 AN: 292

European-Non Finnish (NFE) AF: 0.0968 AC: 6579 AN: 67992

Other (OTH) AF: 0.0697 AC: 147 AN: 2110

Alfa AF: 0.0942 Hom.: 361

Bravo AF: 0.0867

Asia WGS AF: 0.0540 AC: 188 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.58
PhyloP100		-0.063
Mutation Taster		=100/0	polymorphism (auto)

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: rs9895649; hg19: chr17-67258233;