rs58976125

Positions:

• chr7-20647977-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=0.006944716).
• 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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 36 AR gene

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCB5	ENST00000404938.7	c.1105A>G	p.Ile369Val	missense_variant	11/28	1	NM_001163941.2	ENSP00000384881	P1

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

GnomAD3 exomes AF: 0.00322 AC: 794 AN: 246792 Hom.: 12 AF XY: 0.00256 AC XY: 344 AN XY: 134132

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 SAS exome AF: 0.0000330

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

Gnomad4 AFR exome AF: 0.0441

Gnomad4 AMR exome AF: 0.00279

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000817

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000208

Gnomad4 OTH exome AF: 0.00278

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

Gnomad4 AFR AF: 0.0425

Gnomad4 AMR AF: 0.00654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.00228 Hom.: 9

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
MutationTaster	Benign	1.0	D;D;D;D
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

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