chr7-20723163-G-T

Variant names:

• chr7-20723163-G-T
• rs80123476
• NM_001163941.2:c.2569G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001163941.2(ABCB5):​c.2569G>T​(p.Ala857Ser) 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. 16/22 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. A857V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ABCB5 NM_001163941.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.75
• Publications: 6 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060841292).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB5	NM_001163941.2	c.2569G>T	p.Ala857Ser	missense_variant	Exon 21 of 28	ENST00000404938.7	NP_001157413.1
ABCB5	NM_178559.6	c.1234G>T	p.Ala412Ser	missense_variant	Exon 12 of 19		NP_848654.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB5	ENST00000404938.7	c.2569G>T	p.Ala857Ser	missense_variant	Exon 21 of 28	1	NM_001163941.2	ENSP00000384881.2
ABCB5	ENST00000258738.10	c.1234G>T	p.Ala412Ser	missense_variant	Exon 12 of 19	1		ENSP00000258738.6
ABCB5	ENST00000441315.1	n.70G>T		non_coding_transcript_exon_variant	Exon 1 of 8	2		ENSP00000398692.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 251416 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.056	T;.
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.57	T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.061	T;T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	0.60	.;N
PhyloP100		1.7
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.78	N;N
REVEL	Benign	0.14
Sift	Benign	0.063	T;D
Sift4G	Benign	0.11	T;T
Vest4		0.14
MutPred		0.45		.;Gain of disorder (P = 0.0844);
MVP		0.27
MPC		0.0076
ClinPred		0.074	T
GERP RS		0.90
Varity_R		0.065
gMVP		0.33
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs80123476; hg19: chr7-20762786;