rs61732039

chr7-20647981-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001163941.2(ABCB5):c.1109A>G(p.Asp370Gly) variant causes a missense change. The variant allele was found at a frequency of 0.119 in 1,598,770 control chromosomes in the GnomAD database, including 12,606 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 0.097 (921 hom., cov: 33)
  • Exomes 𝑓: 0.12 (11685 hom.)
• Consequence: ABCB5 NM_001163941.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.94

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002119571).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCB5	NM_001163941.2	c.1109A>G	p.Asp370Gly	missense_variant	11/28	ENST00000404938.7
ABCB5	NM_001163942.2	c.-227A>G		5_prime_UTR_variant	2/6
ABCB5	NM_001163993.3	c.-227A>G		5_prime_UTR_variant	2/6
ABCB5	NM_178559.6	c.-227A>G		5_prime_UTR_variant	2/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB5	ENST00000404938.7	c.1109A>G	p.Asp370Gly	missense_variant	11/28	1	NM_001163941.2	P1

Frequencies

GnomAD3 genomes AF: 0.0974 AC: 14819 AN: 152146 Hom.: 921 Cov.: 33

Gnomad AFR AF: 0.0270

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.0931

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0573

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.0865

GnomAD3 exomes AF: 0.103 AC: 25514 AN: 246530 Hom.: 1692 AF XY: 0.106 AC XY: 14173 AN XY: 133974

Gnomad AFR exome AF: 0.0234

Gnomad AMR exome AF: 0.0601

Gnomad ASJ exome AF: 0.118

Gnomad EAS exome AF: 0.00117

Gnomad SAS exome AF: 0.0653

Gnomad FIN exome AF: 0.197

Gnomad NFE exome AF: 0.135

Gnomad OTH exome AF: 0.112

GnomAD4 exome AF: 0.121 AC: 175034 AN: 1446506 Hom.: 11685 Cov.: 29 AF XY: 0.120 AC XY: 86476 AN XY: 720470

Gnomad4 AFR exome AF: 0.0211

Gnomad4 AMR exome AF: 0.0624

Gnomad4 ASJ exome AF: 0.120

Gnomad4 EAS exome AF: 0.000808

Gnomad4 SAS exome AF: 0.0657

Gnomad4 FIN exome AF: 0.192

Gnomad4 NFE exome AF: 0.132

Gnomad4 OTH exome AF: 0.111

GnomAD4 genome AF: 0.0973 AC: 14820 AN: 152264 Hom.: 921 Cov.: 33 AF XY: 0.0986 AC XY: 7342 AN XY: 74442

Gnomad4 AFR AF: 0.0269

Gnomad4 AMR AF: 0.0930

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0578

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.0856

Alfa AF: 0.120 Hom.: 1335

Bravo AF: 0.0866

TwinsUK AF: 0.140 AC: 519

ALSPAC AF: 0.136 AC: 526

ESP6500AA AF: 0.0284 AC: 89

ESP6500EA AF: 0.134 AC: 962

ExAC AF: 0.103 AC: 12379

Asia WGS AF: 0.0270 AC: 93 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.25
Cadd	Uncertain	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.79	T
MetaRNN	Benign	0.0021	T
MetaSVM	Benign	-0.82	T
MutationTaster	Benign	0.99	D;D;D;D
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-5.9	D
REVEL	Pathogenic	0.65
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Vest4		0.12
MPC		0.0095
ClinPred		0.063	T
GERP RS		4.2
Varity_R		0.56
gMVP		0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs61732039; hg19: chr7-20687604; COSMIC: COSV51706664;