rs6461517

Positions:

• chr7-20747650-C-T

Variant summary

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

The ENST00000404938.7(ABCB5):​c.3429+2212C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 152,064 control chromosomes in the GnomAD database, including 9,439 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 0.35 (9439 hom., cov: 32)
• Consequence: ABCB5 ENST00000404938.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCB5	NM_001163941.2	c.3429+2212C>T		intron_variant		ENST00000404938.7	NP_001157413.1
ABCB5	NM_178559.6	c.2094+2212C>T		intron_variant			NP_848654.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCB5	ENST00000404938.7	c.3429+2212C>T		intron_variant		1	NM_001163941.2	ENSP00000384881	P1
ABCB5	ENST00000258738.10	c.2094+2212C>T		intron_variant		1		ENSP00000258738
ABCB5	ENST00000441315.1	c.930+2212C>T		intron_variant, NMD_transcript_variant		2		ENSP00000398692

Frequencies

GnomAD3 genomes AF: 0.349 AC: 53048 AN: 151944 Hom.: 9428 Cov.: 32

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.335

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

GnomAD4 genome AF: 0.349 AC: 53096 AN: 152064 Hom.: 9439 Cov.: 32 AF XY: 0.342 AC XY: 25385 AN XY: 74326

Gnomad4 AFR AF: 0.387

Gnomad4 AMR AF: 0.291

Gnomad4 ASJ AF: 0.422

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.284

Gnomad4 FIN AF: 0.269

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.334

Alfa AF: 0.354 Hom.: 2504

Bravo AF: 0.352

Asia WGS AF: 0.235 AC: 821 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.20
DANN	Benign	0.21

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: rs6461517; hg19: chr7-20787273;