rs76179099

Variant names:

• chr7-20685702-A-G
• NM_001163941.2:c.1876A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-20685702-A-G
• chr7-20685702-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001163941.2(ABCB5):​c.1876A>G​(p.Lys626Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,451,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ABCB5 NM_001163941.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09287855).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB5	NM_001163941.2	c.1876A>G	p.Lys626Glu	missense_variant	Exon 16 of 28	ENST00000404938.7	NP_001157413.1
ABCB5	NM_178559.6	c.541A>G	p.Lys181Glu	missense_variant	Exon 7 of 19		NP_848654.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB5	ENST00000404938.7	c.1876A>G	p.Lys626Glu	missense_variant	Exon 16 of 28	1	NM_001163941.2	ENSP00000384881.2
ABCB5	ENST00000258738.10	c.541A>G	p.Lys181Glu	missense_variant	Exon 7 of 19	1		ENSP00000258738.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1451416 Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1 AN XY: 721980

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000181

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	12
DANN	Benign	0.40
DEOGEN2	Benign	0.031	T;.
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.50	N
LIST_S2	Benign	0.47	T;T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.093	T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	0.54	.;N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.91	N;N
REVEL	Benign	0.25
Sift	Benign	0.66	T;T
Sift4G	Benign	0.59	T;T
Vest4		0.18
MutPred		0.39		.;Loss of ubiquitination at K181 (P = 0.0071);
MVP		0.58
MPC		0.0067
ClinPred		0.10	T
GERP RS		1.7
Varity_R		0.056
gMVP		0.35

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-20725325;