NM_007188.5:c.303C>T

Variant names:

• chr7-151033812-C-T
• rs145393109
• NM_007188.5:c.303C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_007188.5(ABCB8):​c.303C>T​(p.Ala101Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000439 in 1,614,028 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0018 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00030 (2 hom.)
• Consequence: ABCB8 NM_007188.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0490
• Publications: 1 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 7-151033812-C-T is Benign according to our data. Variant chr7-151033812-C-T is described in ClinVar as [Benign]. Clinvar id is 733966.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.049 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB8	NM_007188.5	c.303C>T	p.Ala101Ala	synonymous_variant	Exon 2 of 16	ENST00000358849.9	NP_009119.2
ABCB8	NM_001282291.2	c.354C>T	p.Ala118Ala	synonymous_variant	Exon 3 of 17		NP_001269220.1
ABCB8	NM_001282292.2	c.303C>T	p.Ala101Ala	synonymous_variant	Exon 2 of 16		NP_001269221.1
ABCB8	NM_001282293.2	c.145-461C>T		intron_variant	Intron 1 of 14		NP_001269222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB8	ENST00000358849.9	c.303C>T	p.Ala101Ala	synonymous_variant	Exon 2 of 16	1	NM_007188.5	ENSP00000351717.4

Frequencies

GnomAD3 genomes AF: 0.00179 AC: 272 AN: 152118 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00597

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.000960

GnomAD2 exomes AF: 0.000626 AC: 157 AN: 250654 AF XY: 0.000435

Gnomad AFR exome AF: 0.00585

Gnomad AMR exome AF: 0.000926

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000248

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000299 AC: 437 AN: 1461792 Hom.: 2 Cov.: 30 AF XY: 0.000267 AC XY: 194 AN XY: 727214

African (AFR) AF: 0.00591 AC: 198 AN: 33480

American (AMR) AF: 0.000984 AC: 44 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5764

European-Non Finnish (NFE) AF: 0.000146 AC: 162 AN: 1111974

Other (OTH) AF: 0.000497 AC: 30 AN: 60394

GnomAD4 genome AF: 0.00179 AC: 272 AN: 152236 Hom.: 0 Cov.: 32 AF XY: 0.00173 AC XY: 129 AN XY: 74456

African (AFR) AF: 0.00595 AC: 247 AN: 41528

American (AMR) AF: 0.000915 AC: 14 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68002

Other (OTH) AF: 0.000950 AC: 2 AN: 2106

Alfa AF: 0.000867 Hom.: 0

Bravo AF: 0.00210

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 10, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	8.3
DANN	Benign	0.66
PhyloP100		0.049
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs145393109; hg19: chr7-150730899;