rs6461515

Variant names:

• chr7-20739023-G-A
• rs6461515
• NM_001163941.2:c.2908G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-20739023-G-A
• chr7-20739023-G-C
• chr7-20739023-G-T

Variant summary

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

The NM_001163941.2(ABCB5):​c.2908G>A​(p.Glu970Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.818 in 1,611,028 control chromosomes in the GnomAD database, including 541,196 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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: 𝑓 0.78 (46867 hom., cov: 32)
  • Exomes 𝑓: 0.82 (494329 hom.)
• Consequence: ABCB5 NM_001163941.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.04
• Publications: 39 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 (MetaRNN=9.054558E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB5	NM_001163941.2	c.2908G>A	p.Glu970Lys	missense_variant	Exon 24 of 28	ENST00000404938.7	NP_001157413.1
ABCB5	NM_178559.6	c.1573G>A	p.Glu525Lys	missense_variant	Exon 15 of 19		NP_848654.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB5	ENST00000404938.7	c.2908G>A	p.Glu970Lys	missense_variant	Exon 24 of 28	1	NM_001163941.2	ENSP00000384881.2
ABCB5	ENST00000258738.10	c.1573G>A	p.Glu525Lys	missense_variant	Exon 15 of 19	1		ENSP00000258738.6
ABCB5	ENST00000441315.1	n.409G>A		non_coding_transcript_exon_variant	Exon 4 of 8	2		ENSP00000398692.1

Frequencies

GnomAD3 genomes AF: 0.781 AC: 118647 AN: 152000 Hom.: 46836 Cov.: 32

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.877

Gnomad AMR AF: 0.811

Gnomad ASJ AF: 0.814

Gnomad EAS AF: 0.833

Gnomad SAS AF: 0.723

Gnomad FIN AF: 0.846

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.800

GnomAD2 exomes AF: 0.808 AC: 200324 AN: 247994 AF XY: 0.806

Gnomad AFR exome AF: 0.659

Gnomad AMR exome AF: 0.843

Gnomad ASJ exome AF: 0.810

Gnomad EAS exome AF: 0.818

Gnomad FIN exome AF: 0.854

Gnomad NFE exome AF: 0.827

Gnomad OTH exome AF: 0.816

GnomAD4 exome AF: 0.822 AC: 1199296 AN: 1458910 Hom.: 494329 Cov.: 52 AF XY: 0.820 AC XY: 594753 AN XY: 725660

African (AFR) AF: 0.653 AC: 21744 AN: 33314

American (AMR) AF: 0.842 AC: 37358 AN: 44348

Ashkenazi Jewish (ASJ) AF: 0.808 AC: 21057 AN: 26056

East Asian (EAS) AF: 0.855 AC: 33771 AN: 39492

South Asian (SAS) AF: 0.732 AC: 62735 AN: 85686

European-Finnish (FIN) AF: 0.856 AC: 45664 AN: 53364

Middle Eastern (MID) AF: 0.821 AC: 4720 AN: 5752

European-Non Finnish (NFE) AF: 0.831 AC: 922998 AN: 1110640

Other (OTH) AF: 0.817 AC: 49249 AN: 60258

GnomAD4 genome AF: 0.780 AC: 118728 AN: 152118 Hom.: 46867 Cov.: 32 AF XY: 0.780 AC XY: 58036 AN XY: 74374

African (AFR) AF: 0.664 AC: 27533 AN: 41470

American (AMR) AF: 0.812 AC: 12406 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.814 AC: 2822 AN: 3468

East Asian (EAS) AF: 0.833 AC: 4307 AN: 5168

South Asian (SAS) AF: 0.722 AC: 3481 AN: 4820

European-Finnish (FIN) AF: 0.846 AC: 8961 AN: 10590

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.831 AC: 56482 AN: 67998

Other (OTH) AF: 0.802 AC: 1697 AN: 2116

Alfa AF: 0.812 Hom.: 172923

Bravo AF: 0.776

TwinsUK AF: 0.821 AC: 3043

ALSPAC AF: 0.821 AC: 3163

ESP6500AA AF: 0.666 AC: 2933

ESP6500EA AF: 0.829 AC: 7131

ExAC AF: 0.802 AC: 97349

Asia WGS AF: 0.792 AC: 2755 AN: 3478

EpiCase AF: 0.830

EpiControl AF: 0.824

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.046	T;.
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.85	T;T
MetaRNN	Benign	9.1e-7	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.2	.;L
PhyloP100		2.0
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.20
Sift	Benign	0.10	T;T
Sift4G	Benign	0.27	T;T
Vest4		0.17
MPC		0.012
ClinPred		0.0098	T
GERP RS		4.1
Varity_R		0.11
gMVP		0.70
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs6461515; hg19: chr7-20778646; COSMIC: COSV107257506;