rs34603556

Variant names:

• chr7-20651424-T-C
• rs34603556
• ENST00000258738.10:c.2T>C

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PVS1_Supporting BA1

The ENST00000258738.10(ABCB5):​c.2T>C​(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,613,604 control chromosomes in the GnomAD database, including 32,790 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 0.16 (2326 hom., cov: 32)
  • Exomes 𝑓: 0.20 (30464 hom.)
• Consequence: ABCB5 ENST00000258738.10 start_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.104
• Publications: 23 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 -7 ACMG points.

• PVS1: Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 49 codons. Genomic position: 20651567. Lost 0.059 part of the original CDS.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB5	NM_001163941.2	c.1337T>C	p.Met446Thr	missense_variant	Exon 13 of 28	ENST00000404938.7	NP_001157413.1
ABCB5	NM_178559.6	c.2T>C	p.Met1?	start_lost	Exon 4 of 19		NP_848654.3
ABCB5	NM_001163942.2	c.2T>C	p.Met1?	start_lost	Exon 4 of 6		NP_001157414.1
ABCB5	NM_001163993.3	c.2T>C	p.Met1?	start_lost	Exon 4 of 6		NP_001157465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB5	ENST00000404938.7	c.1337T>C	p.Met446Thr	missense_variant	Exon 13 of 28	1	NM_001163941.2	ENSP00000384881.2

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23985 AN: 152028 Hom.: 2324 Cov.: 32

Gnomad AFR AF: 0.0549

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.0360

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.149

GnomAD2 exomes AF: 0.178 AC: 44665 AN: 250788 AF XY: 0.186

Gnomad AFR exome AF: 0.0527

Gnomad AMR exome AF: 0.0868

Gnomad ASJ exome AF: 0.219

Gnomad EAS exome AF: 0.0345

Gnomad FIN exome AF: 0.304

Gnomad NFE exome AF: 0.210

Gnomad OTH exome AF: 0.187

GnomAD4 exome AF: 0.197 AC: 288465 AN: 1461458 Hom.: 30464 Cov.: 33 AF XY: 0.199 AC XY: 144719 AN XY: 727012

African (AFR) AF: 0.0458 AC: 1532 AN: 33462

American (AMR) AF: 0.0912 AC: 4076 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 5802 AN: 26128

East Asian (EAS) AF: 0.0225 AC: 895 AN: 39690

South Asian (SAS) AF: 0.215 AC: 18542 AN: 86248

European-Finnish (FIN) AF: 0.297 AC: 15842 AN: 53382

Middle Eastern (MID) AF: 0.158 AC: 913 AN: 5766

European-Non Finnish (NFE) AF: 0.206 AC: 229539 AN: 1111706

Other (OTH) AF: 0.188 AC: 11324 AN: 60388

GnomAD4 genome AF: 0.158 AC: 23988 AN: 152146 Hom.: 2326 Cov.: 32 AF XY: 0.162 AC XY: 12034 AN XY: 74358

African (AFR) AF: 0.0549 AC: 2282 AN: 41532

American (AMR) AF: 0.127 AC: 1939 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 763 AN: 3472

East Asian (EAS) AF: 0.0351 AC: 182 AN: 5182

South Asian (SAS) AF: 0.197 AC: 948 AN: 4820

European-Finnish (FIN) AF: 0.303 AC: 3201 AN: 10566

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.208 AC: 14146 AN: 67984

Other (OTH) AF: 0.148 AC: 314 AN: 2116

Alfa AF: 0.188 Hom.: 11025

Bravo AF: 0.138

TwinsUK AF: 0.213 AC: 791

ALSPAC AF: 0.205 AC: 789

ESP6500AA AF: 0.0601 AC: 265

ESP6500EA AF: 0.203 AC: 1749

ExAC AF: 0.180 AC: 21907

Asia WGS AF: 0.0980 AC: 341 AN: 3478

EpiCase AF: 0.209

EpiControl AF: 0.205

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	0.94
DANN	Benign	0.68
DEOGEN2	Benign	0.089	T;.;.;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0063	N
LIST_S2	Benign	0.060	T;D;D;D
MetaRNN	Benign	0.0027	T;T;T;T
MetaSVM	Benign	-0.98	T
PhyloP100		0.10
PrimateAI	Benign	0.36	T
PROVEAN	Benign	2.4	N;N;N;N
REVEL	Benign	0.20
Sift	Benign	1.0	T;D;D;D
Sift4G	Benign	1.0	T;D;D;D
Polyphen		0.19	.;B;.;.
Vest4		0.096
MPC		0.0071
ClinPred		0.0025	T
GERP RS		0.38
Varity_R		0.039
gMVP		0.48
Mutation Taster		=145/55	polymorphism (auto)

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

Other links and lift over

dbSNP: rs34603556; hg19: chr7-20691047; COSMIC: COSV107257505;