chr7-151034543-C-T

Variant names:

• chr7-151034543-C-T
• rs114212581
• NM_007188.5:c.603C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_007188.5(ABCB8):​c.603C>T​(p.His201His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0017 in 1,613,542 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0089 (18 hom., cov: 33)
  • Exomes 𝑓: 0.00095 (20 hom.)
• Consequence: ABCB8 NM_007188.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.273
• 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 7-151034543-C-T is Benign according to our data. Variant chr7-151034543-C-T is described in ClinVar as Benign. ClinVar VariationId is 785238.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.273 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00887 (1351/152276) while in subpopulation AFR AF = 0.0309 (1283/41546). AF 95% confidence interval is 0.0295. There are 18 homozygotes in GnomAd4. There are 651 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 18 AR gene

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.603C>T	p.His201His	synonymous	Exon 4 of 16	NP_009119.2	Q9NUT2-2
	ABCB8	NM_001282291.2		c.654C>T	p.His218His	synonymous	Exon 5 of 17	NP_001269220.1	Q9NUT2-1
	ABCB8	NM_001282292.2		c.603C>T	p.His201His	synonymous	Exon 4 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.603C>T	p.His201His	synonymous	Exon 4 of 16	ENSP00000351717.4	Q9NUT2-2
	ABCB8	ENST00000498578.5	TSL:1	c.603C>T	p.His201His	synonymous	Exon 4 of 16	ENSP00000418271.1	Q9NUT2-3
	ABCB8	ENST00000879589.1		c.735C>T	p.His245His	synonymous	Exon 5 of 17	ENSP00000549648.1

Frequencies

GnomAD3 genomes AF: 0.00885 AC: 1347 AN: 152158 Hom.: 18 Cov.: 33

Gnomad AFR AF: 0.0309

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00268

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00621

GnomAD2 exomes AF: 0.00246 AC: 617 AN: 250746 AF XY: 0.00180

Gnomad AFR exome AF: 0.0333

Gnomad AMR exome AF: 0.00133

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000141

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000947 AC: 1384 AN: 1461266 Hom.: 20 Cov.: 35 AF XY: 0.000821 AC XY: 597 AN XY: 726962

African (AFR) AF: 0.0324 AC: 1084 AN: 33480

American (AMR) AF: 0.00161 AC: 72 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.000479 AC: 19 AN: 39700

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52824

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5768

European-Non Finnish (NFE) AF: 0.0000647 AC: 72 AN: 1112002

Other (OTH) AF: 0.00204 AC: 123 AN: 60382

GnomAD4 genome AF: 0.00887 AC: 1351 AN: 152276 Hom.: 18 Cov.: 33 AF XY: 0.00874 AC XY: 651 AN XY: 74454

African (AFR) AF: 0.0309 AC: 1283 AN: 41546

American (AMR) AF: 0.00268 AC: 41 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5178

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68014

Other (OTH) AF: 0.00615 AC: 13 AN: 2114

Alfa AF: 0.00393 Hom.: 15

Bravo AF: 0.0107

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000237

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	-0.39
CADD	Benign	10
DANN	Benign	0.86
PhyloP100		0.27
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	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: rs114212581; hg19: chr7-150731630;