7-20723314-T-C

Variant names:

• chr7-20723314-T-C
• rs62453385
• NM_001163941.2:c.2625+95T>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.2625+95T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 1,260,398 control chromosomes in the GnomAD database, including 77,791 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 0.30 (7550 hom., cov: 33)
  • Exomes 𝑓: 0.35 (70241 hom.)
• Consequence: ABCB5 NM_001163941.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.45
• Publications: 5 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=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB5	NM_001163941.2	c.2625+95T>C		intron_variant	Intron 21 of 27	ENST00000404938.7	NP_001157413.1
ABCB5	NM_178559.6	c.1290+95T>C		intron_variant	Intron 12 of 18		NP_848654.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB5	ENST00000404938.7	c.2625+95T>C		intron_variant	Intron 21 of 27	1	NM_001163941.2	ENSP00000384881.2
ABCB5	ENST00000258738.10	c.1290+95T>C		intron_variant	Intron 12 of 18	1		ENSP00000258738.6
ABCB5	ENST00000441315.1	n.126+95T>C		intron_variant	Intron 1 of 7	2		ENSP00000398692.1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46258 AN: 152042 Hom.: 7549 Cov.: 33

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.0950

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.324

GnomAD4 exome AF: 0.349 AC: 386871 AN: 1108240 Hom.: 70241 AF XY: 0.350 AC XY: 195396 AN XY: 557974

African (AFR) AF: 0.228 AC: 5798 AN: 25466

American (AMR) AF: 0.213 AC: 7327 AN: 34468

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 8996 AN: 22422

East Asian (EAS) AF: 0.0778 AC: 2707 AN: 34776

South Asian (SAS) AF: 0.334 AC: 23677 AN: 70892

European-Finnish (FIN) AF: 0.223 AC: 8711 AN: 39144

Middle Eastern (MID) AF: 0.382 AC: 1925 AN: 5036

European-Non Finnish (NFE) AF: 0.376 AC: 311490 AN: 827504

Other (OTH) AF: 0.335 AC: 16240 AN: 48532

GnomAD4 genome AF: 0.304 AC: 46268 AN: 152158 Hom.: 7550 Cov.: 33 AF XY: 0.297 AC XY: 22120 AN XY: 74400

African (AFR) AF: 0.234 AC: 9712 AN: 41506

American (AMR) AF: 0.291 AC: 4445 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 1423 AN: 3472

East Asian (EAS) AF: 0.0946 AC: 491 AN: 5190

South Asian (SAS) AF: 0.318 AC: 1531 AN: 4818

European-Finnish (FIN) AF: 0.199 AC: 2111 AN: 10598

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.373 AC: 25349 AN: 67982

Other (OTH) AF: 0.328 AC: 692 AN: 2112

Alfa AF: 0.342 Hom.: 14160

Bravo AF: 0.302

Asia WGS AF: 0.223 AC: 778 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	15
DANN	Benign	0.76
PhyloP100		3.5
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: rs62453385; hg19: chr7-20762937;