7-20647709-C-T

Variant names:

• chr7-20647709-C-T
• rs75784515
• NM_001163941.2:c.1095+61C>T

Variant summary

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

The NM_001163941.2(ABCB5):​c.1095+61C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,526,360 control chromosomes in the GnomAD database, including 31,066 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 0.16 (2313 hom., cov: 32)
  • Exomes 𝑓: 0.20 (28753 hom.)
• Consequence: ABCB5 NM_001163941.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• Publications: 6 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 (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB5	NM_001163941.2	c.1095+61C>T		intron_variant	Intron 10 of 27	ENST00000404938.7	NP_001157413.1
ABCB5	NM_178559.6	c.-241+61C>T		intron_variant	Intron 1 of 18		NP_848654.3
ABCB5	NM_001163942.2	c.-241+61C>T		intron_variant	Intron 1 of 5		NP_001157414.1
ABCB5	NM_001163993.3	c.-241+61C>T		intron_variant	Intron 1 of 5		NP_001157465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB5	ENST00000404938.7	c.1095+61C>T		intron_variant	Intron 10 of 27	1	NM_001163941.2	ENSP00000384881.2

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23896 AN: 151882 Hom.: 2311 Cov.: 32

Gnomad AFR AF: 0.0541

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.0360

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.149

GnomAD4 exome AF: 0.198 AC: 271769 AN: 1374364 Hom.: 28753 AF XY: 0.199 AC XY: 134696 AN XY: 677620

African (AFR) AF: 0.0439 AC: 1312 AN: 29872

American (AMR) AF: 0.0986 AC: 2756 AN: 27954

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 5356 AN: 24286

East Asian (EAS) AF: 0.0207 AC: 738 AN: 35658

South Asian (SAS) AF: 0.213 AC: 15791 AN: 74110

European-Finnish (FIN) AF: 0.297 AC: 14511 AN: 48788

Middle Eastern (MID) AF: 0.160 AC: 823 AN: 5134

European-Non Finnish (NFE) AF: 0.205 AC: 219847 AN: 1071530

Other (OTH) AF: 0.186 AC: 10635 AN: 57032

GnomAD4 genome AF: 0.157 AC: 23899 AN: 151996 Hom.: 2313 Cov.: 32 AF XY: 0.162 AC XY: 12000 AN XY: 74280

African (AFR) AF: 0.0541 AC: 2244 AN: 41458

American (AMR) AF: 0.127 AC: 1937 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 763 AN: 3472

East Asian (EAS) AF: 0.0351 AC: 182 AN: 5178

South Asian (SAS) AF: 0.196 AC: 944 AN: 4820

European-Finnish (FIN) AF: 0.304 AC: 3208 AN: 10536

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14101 AN: 67968

Other (OTH) AF: 0.148 AC: 313 AN: 2114

Alfa AF: 0.0826 Hom.: 153

Bravo AF: 0.137

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.80
DANN	Benign	0.64
PhyloP100		-1.2
PromoterAI		0.0010	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs75784515; hg19: chr7-20687332;