7-20647977-A-G

Variant names:

• chr7-20647977-A-G
• rs58976125
• NM_001163941.2:c.1105A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001163941.2(ABCB5):​c.1105A>G​(p.Ile369Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00245 in 1,591,768 control chromosomes in the GnomAD database, including 70 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 0.013 (36 hom., cov: 33)
  • Exomes 𝑓: 0.0014 (34 hom.)
• Consequence: ABCB5 NM_001163941.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.72
• Publications: 9 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=0.006944716).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0125 (1907/152334) while in subpopulation AFR AF = 0.0425 (1766/41578). AF 95% confidence interval is 0.0408. There are 36 homozygotes in GnomAd4. There are 914 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 36 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB5	NM_001163941.2	c.1105A>G	p.Ile369Val	missense_variant	Exon 11 of 28	ENST00000404938.7	NP_001157413.1
ABCB5	NM_178559.6	c.-231A>G		5_prime_UTR_variant	Exon 2 of 19		NP_848654.3
ABCB5	NM_001163942.2	c.-231A>G		5_prime_UTR_variant	Exon 2 of 6		NP_001157414.1
ABCB5	NM_001163993.3	c.-231A>G		5_prime_UTR_variant	Exon 2 of 6		NP_001157465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB5	ENST00000404938.7	c.1105A>G	p.Ile369Val	missense_variant	Exon 11 of 28	1	NM_001163941.2	ENSP00000384881.2

Frequencies

GnomAD3 genomes AF: 0.0124 AC: 1888 AN: 152216 Hom.: 32 Cov.: 33

Gnomad AFR AF: 0.0421

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.0110

GnomAD2 exomes AF: 0.00322 AC: 794 AN: 246792 AF XY: 0.00256

Gnomad AFR exome AF: 0.0442

Gnomad AMR exome AF: 0.00226

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000215

Gnomad OTH exome AF: 0.00233

GnomAD4 exome AF: 0.00139 AC: 1996 AN: 1439434 Hom.: 34 Cov.: 28 AF XY: 0.00123 AC XY: 886 AN XY: 717636

African (AFR) AF: 0.0441 AC: 1455 AN: 33022

American (AMR) AF: 0.00279 AC: 124 AN: 44434

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25964

East Asian (EAS) AF: 0.00 AC: 0 AN: 39558

South Asian (SAS) AF: 0.0000817 AC: 7 AN: 85670

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53344

Middle Eastern (MID) AF: 0.00299 AC: 17 AN: 5692

European-Non Finnish (NFE) AF: 0.000208 AC: 227 AN: 1092140

Other (OTH) AF: 0.00278 AC: 166 AN: 59610

GnomAD4 genome AF: 0.0125 AC: 1907 AN: 152334 Hom.: 36 Cov.: 33 AF XY: 0.0123 AC XY: 914 AN XY: 74476

African (AFR) AF: 0.0425 AC: 1766 AN: 41578

American (AMR) AF: 0.00654 AC: 100 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68032

Other (OTH) AF: 0.0109 AC: 23 AN: 2116

Alfa AF: 0.00340 Hom.: 25

Bravo AF: 0.0142

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.0408 AC: 128

ESP6500EA AF: 0.000279 AC: 2

ExAC AF: 0.00383 AC: 460

Asia WGS AF: 0.00404 AC: 15 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	22
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.068	T
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
MetaRNN	Benign	0.0069	T
MetaSVM	Uncertain	0.23	D
PhyloP100		8.7
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.89	N
REVEL	Uncertain	0.62
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Vest4		0.41
MVP		0.89
MPC		0.044
ClinPred		0.033	T
GERP RS		5.3
Varity_R		0.16
gMVP		0.36
Mutation Taster		=195/105	polymorphism

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: rs58976125; hg19: chr7-20687600; COSMIC: COSV51712786;