rs149897534

Variant names:

• chr7-151033839-C-T
• rs149897534
• NM_007188.5:c.330C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_007188.5(ABCB8):​c.330C>T​(p.Val110Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000267 in 1,613,890 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0012 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: ABCB8 NM_007188.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.39
• Publications: 2 publications found

Genes affected

ABCB8 (HGNC:49): (ATP binding cassette subfamily B member 8) This nuclear gene encodes a multi-pass membrane protein that is targeted to the mitochondrial inner membrane. The encoded protein is an ATP-dependent transporter that may mediate the passage of organic and inorganic molecules out of the mitochondria. Loss of function of the related gene in mouse results in a disruption of iron homeostasis between the mitochondria and cytosol. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 7-151033839-C-T is Benign according to our data. Variant chr7-151033839-C-T is described in ClinVar as Benign. ClinVar VariationId is 727305.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.39 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007188.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB8	NM_007188.5	MANE Select	c.330C>T	p.Val110Val	synonymous	Exon 2 of 16	NP_009119.2	Q9NUT2-2
	ABCB8	NM_001282291.2		c.381C>T	p.Val127Val	synonymous	Exon 3 of 17	NP_001269220.1	Q9NUT2-1
	ABCB8	NM_001282292.2		c.330C>T	p.Val110Val	synonymous	Exon 2 of 16	NP_001269221.1	Q9NUT2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB8	ENST00000358849.9	TSL:1 MANE Select	c.330C>T	p.Val110Val	synonymous	Exon 2 of 16	ENSP00000351717.4	Q9NUT2-2
	ABCB8	ENST00000498578.5	TSL:1	c.330C>T	p.Val110Val	synonymous	Exon 2 of 16	ENSP00000418271.1	Q9NUT2-3
	ABCB8	ENST00000879589.1		c.462C>T	p.Val154Val	synonymous	Exon 3 of 17	ENSP00000549648.1

Frequencies

GnomAD3 genomes AF: 0.00125 AC: 190 AN: 152156 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00192

GnomAD2 exomes AF: 0.000464 AC: 116 AN: 249882 AF XY: 0.000266

Gnomad AFR exome AF: 0.00652

Gnomad AMR exome AF: 0.000203

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000328

GnomAD4 exome AF: 0.000166 AC: 242 AN: 1461616 Hom.: 0 Cov.: 31 AF XY: 0.000142 AC XY: 103 AN XY: 727110

African (AFR) AF: 0.00603 AC: 202 AN: 33478

American (AMR) AF: 0.000246 AC: 11 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00000809 AC: 9 AN: 1111912

Other (OTH) AF: 0.000265 AC: 16 AN: 60382

GnomAD4 genome AF: 0.00124 AC: 189 AN: 152274 Hom.: 1 Cov.: 33 AF XY: 0.00137 AC XY: 102 AN XY: 74464

African (AFR) AF: 0.00433 AC: 180 AN: 41550

American (AMR) AF: 0.000196 AC: 3 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67996

Other (OTH) AF: 0.00190 AC: 4 AN: 2110

Alfa AF: 0.000818 Hom.: 0

Bravo AF: 0.00154

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.47
DANN	Benign	0.58
PhyloP100		-2.4

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: rs149897534; hg19: chr7-150730926;