chr7-20660738-A-C

Variant names:

• chr7-20660738-A-C
• rs6952128
• NM_001163941.2:c.1707+2062A>C

Variant summary

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

The NM_001163941.2(ABCB5):​c.1707+2062A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 151,964 control chromosomes in the GnomAD database, including 14,023 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 0.41 (14023 hom., cov: 32)
• Consequence: ABCB5 NM_001163941.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0340
• Publications: 2 publications found

Genes affected

ABCB5 (HGNC:46): (ATP binding cassette subfamily B member 5) ABCB5 belongs to the ATP-binding cassette (ABC) transporter superfamily of integral membrane proteins. These proteins participate in ATP-dependent transmembrane transport of structurally diverse molecules ranging from small ions, sugars, and peptides to more complex organic molecules (Chen et al., 2005 [PubMed 15760339]).[supplied by OMIM, Mar 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB5	NM_001163941.2	c.1707+2062A>C		intron_variant	Intron 14 of 27	ENST00000404938.7	NP_001157413.1
ABCB5	NM_178559.6	c.372+2062A>C		intron_variant	Intron 5 of 18		NP_848654.3
ABCB5	NM_001163993.3	c.372+2062A>C		intron_variant	Intron 5 of 5		NP_001157465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB5	ENST00000404938.7	c.1707+2062A>C		intron_variant	Intron 14 of 27	1	NM_001163941.2	ENSP00000384881.2
ABCB5	ENST00000258738.10	c.372+2062A>C		intron_variant	Intron 5 of 18	1		ENSP00000258738.6
ABCB5	ENST00000406935.5	c.372+2062A>C		intron_variant	Intron 5 of 5	2		ENSP00000383899.1

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61535 AN: 151846 Hom.: 13996 Cov.: 32

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.353

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

GnomAD4 genome AF: 0.405 AC: 61618 AN: 151964 Hom.: 14023 Cov.: 32 AF XY: 0.405 AC XY: 30049 AN XY: 74284

African (AFR) AF: 0.631 AC: 26143 AN: 41426

American (AMR) AF: 0.353 AC: 5396 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 1105 AN: 3466

East Asian (EAS) AF: 0.245 AC: 1266 AN: 5162

South Asian (SAS) AF: 0.326 AC: 1567 AN: 4814

European-Finnish (FIN) AF: 0.349 AC: 3682 AN: 10558

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.316 AC: 21444 AN: 67952

Other (OTH) AF: 0.353 AC: 745 AN: 2108

Alfa AF: 0.337 Hom.: 28778

Bravo AF: 0.413

Asia WGS AF: 0.298 AC: 1037 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.8
DANN	Benign	0.67
PhyloP100		-0.034
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: rs6952128; hg19: chr7-20700361;