rs2301641

Variant names:

• chr7-20658647-A-C
• rs2301641
• NM_001163941.2:c.1678A>C

Your query was ambiguous. Multiple possible variants found:

• chr7-20658647-A-C
• chr7-20658647-A-G
• chr7-20658647-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001163941.2(ABCB5):​c.1678A>C​(p.Lys560Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,804 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ABCB5 NM_001163941.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.85
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001163941.2. 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
	ABCB5	NM_001163941.2	MANE Select	c.1678A>C	p.Lys560Gln	missense	Exon 14 of 28	NP_001157413.1	Q2M3G0-4
	ABCB5	NM_178559.6		c.343A>C	p.Lys115Gln	missense	Exon 5 of 19	NP_848654.3
	ABCB5	NM_001163942.2		c.343A>C	p.Lys115Gln	missense	Exon 5 of 6	NP_001157414.1	Q2M3G0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB5	ENST00000404938.7	TSL:1 MANE Select	c.1678A>C	p.Lys560Gln	missense	Exon 14 of 28	ENSP00000384881.2	Q2M3G0-4
	ABCB5	ENST00000258738.10	TSL:1	c.343A>C	p.Lys115Gln	missense	Exon 5 of 19	ENSP00000258738.6	Q2M3G0-1
	ABCB5	ENST00000443026.6	TSL:1	c.343A>C	p.Lys115Gln	missense	Exon 5 of 6	ENSP00000406730.2	Q2M3G0-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461804 Hom.: 0 Cov.: 38 AF XY: 0.00 AC XY: 0 AN XY: 727204

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111974

Other (OTH) AF: 0.0000166 AC: 1 AN: 60390

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Uncertain	0.018	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.064	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.32
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.056	D
MetaRNN	Uncertain	0.50	T
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Benign	-0.41	N
PhyloP100		6.9
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	0.86	N
REVEL	Uncertain	0.38
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.0030	B
Vest4		0.22
MutPred		0.83		Loss of ubiquitination at K115 (P = 0.0161)
MVP		0.74
MPC		0.0073
ClinPred		0.85	D
GERP RS		4.7
Varity_R		0.27
gMVP		0.38
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2301641; hg19: chr7-20698270;