rs6950237

Positions:

• chr7-20648512-G-A
• chr7-20648512-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001163941.2(ABCB5):​c.1206+434G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 151,816 control chromosomes in the GnomAD database, including 10,396 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 0.36 (10396 hom., cov: 32)
• Consequence: ABCB5 NM_001163941.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.629

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 (BayesDel_noAF=-1.06).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCB5	NM_001163941.2	c.1206+434G>A		intron_variant		ENST00000404938.7	NP_001157413.1
ABCB5	NM_001163942.2	c.-130+434G>A		intron_variant			NP_001157414.1
ABCB5	NM_001163993.3	c.-130+434G>A		intron_variant			NP_001157465.1
ABCB5	NM_178559.6	c.-130+434G>A		intron_variant			NP_848654.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCB5	ENST00000404938.7	c.1206+434G>A		intron_variant		1	NM_001163941.2	ENSP00000384881	P1

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54128 AN: 151698 Hom.: 10371 Cov.: 32

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.313

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.357 AC: 54204 AN: 151816 Hom.: 10396 Cov.: 32 AF XY: 0.357 AC XY: 26511 AN XY: 74192

Gnomad4 AFR AF: 0.503

Gnomad4 AMR AF: 0.327

Gnomad4 ASJ AF: 0.299

Gnomad4 EAS AF: 0.190

Gnomad4 SAS AF: 0.315

Gnomad4 FIN AF: 0.363

Gnomad4 NFE AF: 0.296

Gnomad4 OTH AF: 0.313

Alfa AF: 0.302 Hom.: 8865

Bravo AF: 0.358

Asia WGS AF: 0.272 AC: 947 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.3
DANN	Benign	0.79

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: rs6950237; hg19: chr7-20688135;