7-20739023-G-C

Position:

• chr7-20739023-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001163941.2(ABCB5):​c.2908G>C​(p.Glu970Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E970K) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ABCB5 NM_001163941.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.04

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05841598).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCB5	NM_001163941.2	c.2908G>C	p.Glu970Gln	missense_variant	24/28	ENST00000404938.7	NP_001157413.1
ABCB5	NM_178559.6	c.1573G>C	p.Glu525Gln	missense_variant	15/19		NP_848654.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCB5	ENST00000404938.7	c.2908G>C	p.Glu970Gln	missense_variant	24/28	1	NM_001163941.2	ENSP00000384881	P1
ABCB5	ENST00000258738.10	c.1573G>C	p.Glu525Gln	missense_variant	15/19	1		ENSP00000258738
ABCB5	ENST00000441315.1	c.409G>C	p.Glu137Gln	missense_variant, NMD_transcript_variant	4/8	2		ENSP00000398692

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 52

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	17
DANN	Benign	0.092
DEOGEN2	Benign	0.033	T;.
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.65	T;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.058	T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	-0.57	.;N
MutationTaster	Benign	0.94	P;P
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.87	N;N
REVEL	Benign	0.20
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Vest4		0.19
MutPred		0.48		.;Gain of helix (P = 0.132);
MVP		0.33
MPC		0.0096
ClinPred		0.089	T
GERP RS		4.1
Varity_R		0.065
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs6461515; hg19: chr7-20778646;