7-20643261-C-T

Variant names:

• chr7-20643261-C-T
• rs17143212
• NM_001163941.2:c.392C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001163941.2(ABCB5):​c.392C>T​(p.Thr131Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0338 in 1,613,684 control chromosomes in the GnomAD database, including 1,312 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 0.041 (199 hom., cov: 33)
  • Exomes 𝑓: 0.033 (1113 hom.)
• Consequence: ABCB5 NM_001163941.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.82
• Publications: 17 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.101 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.392C>T	p.Thr131Ile	missense	Exon 6 of 28	NP_001157413.1	Q2M3G0-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB5	ENST00000404938.7	TSL:1 MANE Select	c.392C>T	p.Thr131Ile	missense	Exon 6 of 28	ENSP00000384881.2	Q2M3G0-4

Frequencies

GnomAD3 genomes AF: 0.0415 AC: 6313 AN: 152144 Hom.: 199 Cov.: 33

Gnomad AFR AF: 0.0678

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0201

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.0911

Gnomad FIN AF: 0.0188

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0275

Gnomad OTH AF: 0.0244

GnomAD2 exomes AF: 0.0390 AC: 9678 AN: 248226 AF XY: 0.0409

Gnomad AFR exome AF: 0.0715

Gnomad AMR exome AF: 0.00971

Gnomad ASJ exome AF: 0.0122

Gnomad EAS exome AF: 0.111

Gnomad FIN exome AF: 0.0167

Gnomad NFE exome AF: 0.0283

Gnomad OTH exome AF: 0.0273

GnomAD4 exome AF: 0.0330 AC: 48217 AN: 1461422 Hom.: 1113 Cov.: 31 AF XY: 0.0344 AC XY: 24976 AN XY: 726944

African (AFR) AF: 0.0764 AC: 2558 AN: 33480

American (AMR) AF: 0.0101 AC: 451 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 300 AN: 26132

East Asian (EAS) AF: 0.0930 AC: 3690 AN: 39676

South Asian (SAS) AF: 0.0785 AC: 6768 AN: 86220

European-Finnish (FIN) AF: 0.0182 AC: 970 AN: 53394

Middle Eastern (MID) AF: 0.0355 AC: 205 AN: 5768

European-Non Finnish (NFE) AF: 0.0281 AC: 31278 AN: 1111720

Other (OTH) AF: 0.0331 AC: 1997 AN: 60364

GnomAD4 genome AF: 0.0415 AC: 6317 AN: 152262 Hom.: 199 Cov.: 33 AF XY: 0.0421 AC XY: 3135 AN XY: 74426

African (AFR) AF: 0.0678 AC: 2815 AN: 41544

American (AMR) AF: 0.0201 AC: 307 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0124 AC: 43 AN: 3472

East Asian (EAS) AF: 0.108 AC: 561 AN: 5182

South Asian (SAS) AF: 0.0906 AC: 437 AN: 4824

European-Finnish (FIN) AF: 0.0188 AC: 199 AN: 10612

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0274 AC: 1867 AN: 68024

Other (OTH) AF: 0.0241 AC: 51 AN: 2114

Alfa AF: 0.0324 Hom.: 337

Bravo AF: 0.0409

TwinsUK AF: 0.0299 AC: 111

ALSPAC AF: 0.0267 AC: 103

ESP6500AA AF: 0.0727 AC: 228

ESP6500EA AF: 0.0274 AC: 196

ExAC AF: 0.0416 AC: 5012

EpiCase AF: 0.0269

EpiControl AF: 0.0265

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.026
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.54	D
LIST_S2	Uncertain	0.90	D
MetaRNN	Benign	0.0032	T
MetaSVM	Benign	-0.94	T
PhyloP100		4.8
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.34
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.081	T
Vest4		0.10
MPC		0.020
ClinPred		0.048	T
GERP RS		3.0
Varity_R		0.24
gMVP		0.55
Mutation Taster		=84/16	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.25		Position offset: 6

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17143212; hg19: chr7-20682884; COSMIC: COSV51708582; COSMIC: COSV51708582;