rs35885925

Variant names:

• chr7-20727129-G-T
• rs35885925
• NM_001163941.2:c.2715G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-20727129-G-T
• chr7-20727129-G-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001163941.2(ABCB5):​c.2715G>T​(p.Gln905His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00337 in 1,612,608 control chromosomes in the GnomAD database, including 166 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (81 hom., cov: 33)
  • Exomes 𝑓: 0.0018 (85 hom.)
• Consequence: ABCB5 NM_001163941.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.26
• Publications: 7 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0028603375).
• BP6: Variant 7-20727129-G-T is Benign according to our data. Variant chr7-20727129-G-T is described in ClinVar as Benign. ClinVar VariationId is 784107.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0607 is higher than 0.05.

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.2715G>T	p.Gln905His	missense	Exon 22 of 28	NP_001157413.1	Q2M3G0-4
	ABCB5	NM_178559.6		c.1380G>T	p.Gln460His	missense	Exon 13 of 19	NP_848654.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB5	ENST00000404938.7	TSL:1 MANE Select	c.2715G>T	p.Gln905His	missense	Exon 22 of 28	ENSP00000384881.2	Q2M3G0-4
	ABCB5	ENST00000258738.10	TSL:1	c.1380G>T	p.Gln460His	missense	Exon 13 of 19	ENSP00000258738.6	Q2M3G0-1
	ABCB5	ENST00000441315.1	TSL:2	n.216G>T		non_coding_transcript_exon	Exon 2 of 8	ENSP00000398692.1	H7C165

Frequencies

GnomAD3 genomes AF: 0.0180 AC: 2741 AN: 152152 Hom.: 81 Cov.: 33

Gnomad AFR AF: 0.0627

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00603

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.0163

GnomAD2 exomes AF: 0.00487 AC: 1218 AN: 250122 AF XY: 0.00341

Gnomad AFR exome AF: 0.0682

Gnomad AMR exome AF: 0.00270

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000532

Gnomad OTH exome AF: 0.00197

GnomAD4 exome AF: 0.00184 AC: 2692 AN: 1460338 Hom.: 85 Cov.: 29 AF XY: 0.00149 AC XY: 1080 AN XY: 726594

African (AFR) AF: 0.0671 AC: 2240 AN: 33406

American (AMR) AF: 0.00291 AC: 130 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39612

South Asian (SAS) AF: 0.000128 AC: 11 AN: 86198

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53276

Middle Eastern (MID) AF: 0.00174 AC: 10 AN: 5754

European-Non Finnish (NFE) AF: 0.0000387 AC: 43 AN: 1110968

Other (OTH) AF: 0.00428 AC: 258 AN: 60332

GnomAD4 genome AF: 0.0180 AC: 2748 AN: 152270 Hom.: 81 Cov.: 33 AF XY: 0.0172 AC XY: 1279 AN XY: 74456

African (AFR) AF: 0.0627 AC: 2605 AN: 41552

American (AMR) AF: 0.00602 AC: 92 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000827 AC: 4 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68020

Other (OTH) AF: 0.0161 AC: 34 AN: 2114

Alfa AF: 0.00693 Hom.: 79

Bravo AF: 0.0207

ESP6500AA AF: 0.0613 AC: 270

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00575 AC: 698

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	17
DANN	Benign	0.89
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.31
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.077	T
MetaRNN	Benign	0.0029	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.3
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.20
Sift	Benign	0.14	T
Sift4G	Benign	0.12	T
Vest4		0.23
MutPred		0.41		Loss of MoRF binding (P = 0.1756)
MVP		0.40
MPC		0.0075
ClinPred		0.0058	T
GERP RS		1.6
Varity_R		0.13
gMVP		0.30
Mutation Taster		=92/8	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: rs35885925; hg19: chr7-20766752; COSMIC: COSV51715845;