rs60197951

Variant names:

• chr7-20745287-T-C
• rs60197951
• NM_001163941.2:c.3278T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001163941.2(ABCB5):​c.3278T>C​(p.Ile1093Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00606 in 1,614,014 control chromosomes in the GnomAD database, including 179 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 0.018 (65 hom., cov: 33)
  • Exomes 𝑓: 0.0048 (114 hom.)
• Consequence: ABCB5 NM_001163941.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.24
• Publications: 10 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=0.00996232).
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0578 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.3278T>C	p.Ile1093Thr	missense	Exon 26 of 28	NP_001157413.1
	ABCB5	NM_178559.6		c.1943T>C	p.Ile648Thr	missense	Exon 17 of 19	NP_848654.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB5	ENST00000404938.7	TSL:1 MANE Select	c.3278T>C	p.Ile1093Thr	missense	Exon 26 of 28	ENSP00000384881.2
	ABCB5	ENST00000258738.10	TSL:1	c.1943T>C	p.Ile648Thr	missense	Exon 17 of 19	ENSP00000258738.6
	ABCB5	ENST00000441315.1	TSL:2	n.779T>C		non_coding_transcript_exon	Exon 6 of 8	ENSP00000398692.1

Frequencies

GnomAD3 genomes AF: 0.0180 AC: 2739 AN: 152160 Hom.: 65 Cov.: 33

Gnomad AFR AF: 0.0515

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0163

Gnomad ASJ AF: 0.0302

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.00276

Gnomad OTH AF: 0.0239

GnomAD2 exomes AF: 0.00837 AC: 2103 AN: 251280 AF XY: 0.00714

Gnomad AFR exome AF: 0.0524

Gnomad AMR exome AF: 0.0102

Gnomad ASJ exome AF: 0.0306

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00394

Gnomad OTH exome AF: 0.0161

GnomAD4 exome AF: 0.00482 AC: 7040 AN: 1461736 Hom.: 114 Cov.: 31 AF XY: 0.00475 AC XY: 3452 AN XY: 727176

African (AFR) AF: 0.0600 AC: 2008 AN: 33474

American (AMR) AF: 0.0112 AC: 503 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0309 AC: 808 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00137 AC: 118 AN: 86250

European-Finnish (FIN) AF: 0.0000936 AC: 5 AN: 53420

Middle Eastern (MID) AF: 0.0401 AC: 231 AN: 5758

European-Non Finnish (NFE) AF: 0.00243 AC: 2700 AN: 1111904

Other (OTH) AF: 0.0110 AC: 667 AN: 60378

GnomAD4 genome AF: 0.0180 AC: 2746 AN: 152278 Hom.: 65 Cov.: 33 AF XY: 0.0179 AC XY: 1336 AN XY: 74478

African (AFR) AF: 0.0515 AC: 2139 AN: 41536

American (AMR) AF: 0.0162 AC: 248 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0302 AC: 105 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.00276 AC: 188 AN: 68016

Other (OTH) AF: 0.0237 AC: 50 AN: 2110

Alfa AF: 0.0100 Hom.: 58

Bravo AF: 0.0215

TwinsUK AF: 0.00270 AC: 10

ALSPAC AF: 0.00156 AC: 6

ESP6500AA AF: 0.0561 AC: 247

ESP6500EA AF: 0.00349 AC: 30

ExAC AF: 0.00852 AC: 1035

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.00545

EpiControl AF: 0.00563

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	20
DANN	Benign	0.93
DEOGEN2	Uncertain	0.46	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.38
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.85	T
MetaRNN	Benign	0.010	T
MetaSVM	Benign	-0.28	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		4.2
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.40
Sift	Benign	0.060	T
Sift4G	Uncertain	0.030	D
Vest4		0.47
MVP		0.42
MPC		0.0071
ClinPred		0.068	T
GERP RS		0.31
Varity_R		0.16
gMVP		0.74
Mutation Taster		=93/7	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs60197951; hg19: chr7-20784910; COSMIC: COSV51708600;