7-20647981-A-G

Variant names:

• chr7-20647981-A-G
• rs61732039
• NM_001163941.2:c.1109A>G

Variant summary

Our verdict is Benign. The variant received -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
• 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 -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB5	NM_001163941.2	MANE Select	c.1109A>G	p.Asp370Gly	missense	Exon 11 of 28	NP_001157413.1
	ABCB5	NM_178559.6		c.-227A>G		5_prime_UTR	Exon 2 of 19	NP_848654.3
	ABCB5	NM_001163942.2		c.-227A>G		5_prime_UTR	Exon 2 of 6	NP_001157414.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB5	ENST00000404938.7	TSL:1 MANE Select	c.1109A>G	p.Asp370Gly	missense	Exon 11 of 28	ENSP00000384881.2
	ABCB5	ENST00000258738.10	TSL:1	c.-227A>G		5_prime_UTR	Exon 2 of 19	ENSP00000258738.6
	ABCB5	ENST00000443026.6	TSL:1	c.-227A>G		5_prime_UTR	Exon 2 of 6	ENSP00000406730.2

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

GnomAD2 exomes AF: 0.103 AC: 25514 AN: 246530 AF XY: 0.106

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 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

African (AFR) AF: 0.0211 AC: 700 AN: 33202

American (AMR) AF: 0.0624 AC: 2770 AN: 44400

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 3127 AN: 26018

East Asian (EAS) AF: 0.000808 AC: 32 AN: 39594

South Asian (SAS) AF: 0.0657 AC: 5637 AN: 85826

European-Finnish (FIN) AF: 0.192 AC: 10227 AN: 53344

Middle Eastern (MID) AF: 0.102 AC: 580 AN: 5708

European-Non Finnish (NFE) AF: 0.132 AC: 145293 AN: 1098574

Other (OTH) AF: 0.111 AC: 6668 AN: 59840

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

African (AFR) AF: 0.0269 AC: 1120 AN: 41576

American (AMR) AF: 0.0930 AC: 1421 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 405 AN: 3470

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5186

South Asian (SAS) AF: 0.0578 AC: 279 AN: 4830

European-Finnish (FIN) AF: 0.198 AC: 2102 AN: 10596

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9140 AN: 68000

Other (OTH) AF: 0.0856 AC: 181 AN: 2114

Alfa AF: 0.118 Hom.: 3125

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 v4.9

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
PhyloP100		6.9
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
Mutation Taster		=192/108	polymorphism (auto)

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

Other links and lift over

dbSNP: rs61732039; hg19: chr7-20687604; COSMIC: COSV51706664;