rs34603556

chr7-20651424-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 8P and 8B. PVS1 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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PVS1: Start lost variant, no new inframe start found.
• 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/exons	MANE	UniProt
ABCB5	NM_001163941.2	c.1337T>C	p.Met446Thr	missense_variant	13/28	ENST00000404938.7
ABCB5	NM_178559.6	c.2T>C	p.Met1?	start_lost	4/19
ABCB5	NM_001163942.2	c.2T>C	p.Met1?	start_lost	4/6
ABCB5	NM_001163993.3	c.2T>C	p.Met1?	start_lost	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB5	ENST00000404938.7	c.1337T>C	p.Met446Thr	missense_variant	13/28	1	NM_001163941.2	P1

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

GnomAD3 exomes AF: 0.178 AC: 44665 AN: 250788 Hom.: 4868 AF XY: 0.186 AC XY: 25271 AN XY: 135522

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 SAS exome AF: 0.211

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

Gnomad4 AFR exome AF: 0.0458

Gnomad4 AMR exome AF: 0.0912

Gnomad4 ASJ exome AF: 0.222

Gnomad4 EAS exome AF: 0.0225

Gnomad4 SAS exome AF: 0.215

Gnomad4 FIN exome AF: 0.297

Gnomad4 NFE exome AF: 0.206

Gnomad4 OTH exome AF: 0.188

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

Gnomad4 AFR AF: 0.0549

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.0351

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.303

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.148

Alfa AF: 0.191 Hom.: 5536

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
MutationTaster	Benign	5.0e-17	P;P;P;P
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

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

Publications

LitVar

Other links and lift over

dbSNP: rs34603556; hg19: chr7-20691047;