7-20645746-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001163941.2(ABCB5):c.679-10T>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00296 in 1,613,400 control chromosomes in the GnomAD database, including 118 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (60 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (58 hom.)
• Consequence: ABCB5 NM_001163941.2 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.4946
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0540

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 7-20645746-T-G is Benign according to our data. Variant chr7-20645746-T-G is described in ClinVar as [Benign]. Clinvar id is 776209.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCB5	NM_001163941.2	c.679-10T>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000404938.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB5	ENST00000404938.7	c.679-10T>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001163941.2	P1

Frequencies

GnomAD3 genomes AF: 0.0162 AC: 2460 AN: 152170 Hom.: 61 Cov.: 33

Gnomad AFR AF: 0.0559

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.0105

GnomAD3 exomes AF: 0.00417 AC: 1035 AN: 248160 Hom.: 29 AF XY: 0.00323 AC XY: 436 AN XY: 134826

Gnomad AFR exome AF: 0.0587

Gnomad AMR exome AF: 0.00279

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000656

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000125

Gnomad OTH exome AF: 0.00282

GnomAD4 exome AF: 0.00158 AC: 2313 AN: 1461112 Hom.: 58 Cov.: 30 AF XY: 0.00132 AC XY: 963 AN XY: 726796

Gnomad4 AFR exome AF: 0.0538

Gnomad4 AMR exome AF: 0.00385

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000929

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000864

Gnomad4 OTH exome AF: 0.00353

GnomAD4 genome AF: 0.0162 AC: 2470 AN: 152288 Hom.: 60 Cov.: 33 AF XY: 0.0157 AC XY: 1166 AN XY: 74454

Gnomad4 AFR AF: 0.0560

Gnomad4 AMR AF: 0.00654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000250

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.00880 Hom.: 10

Bravo AF: 0.0180

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 12, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	14
Dann	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.49
dbscSNV1_RF	Benign	0.43
SpliceAI score (max)		0.39		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.39		Position offset: 10

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs77094935; hg19: chr7-20685369;