chr7-20739023-G-T

Variant names:

• chr7-20739023-G-T
• rs6461515
• NM_001163941.2:c.2908G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001163941.2(ABCB5):​c.2908G>T​(p.Glu970*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ABCB5 NM_001163941.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.04
• Publications: 39 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.2908G>T	p.Glu970*	stop_gained	Exon 24 of 28	NP_001157413.1
	ABCB5	NM_178559.6		c.1573G>T	p.Glu525*	stop_gained	Exon 15 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.2908G>T	p.Glu970*	stop_gained	Exon 24 of 28	ENSP00000384881.2
	ABCB5	ENST00000258738.10	TSL:1	c.1573G>T	p.Glu525*	stop_gained	Exon 15 of 19	ENSP00000258738.6
	ABCB5	ENST00000441315.1	TSL:2	n.409G>T		non_coding_transcript_exon	Exon 4 of 8	ENSP00000398692.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 52

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.49	D
BayesDel_noAF	Pathogenic	0.47
CADD	Pathogenic	42
DANN	Uncertain	1.0
Eigen	Pathogenic	0.72
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.76	D
PhyloP100		2.0
Vest4		0.70
GERP RS		4.1
Mutation Taster		=54/146	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.27		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.27		Position offset: -40

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

Other links and lift over

dbSNP: rs6461515; hg19: chr7-20778646;