7-151034432-C-T

Variant names:

• chr7-151034432-C-T
• rs7776772
• NM_007188.5:c.564+4C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_007188.5(ABCB8):​c.564+4C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00416 in 1,613,872 control chromosomes in the GnomAD database, including 107 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (42 hom., cov: 33)
  • Exomes 𝑓: 0.0029 (65 hom.)
• Consequence: ABCB8 NM_007188.5 splice_region, intron
• Scores: Splicing: ADA: 0.0002467
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.144
• Publications: 0 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 7-151034432-C-T is Benign according to our data. Variant chr7-151034432-C-T is described in ClinVar as [Benign]. Clinvar id is 773219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB8	NM_007188.5	c.564+4C>T		splice_region_variant, intron_variant	Intron 3 of 15	ENST00000358849.9	NP_009119.2
ABCB8	NM_001282291.2	c.615+4C>T		splice_region_variant, intron_variant	Intron 4 of 16		NP_001269220.1
ABCB8	NM_001282292.2	c.564+4C>T		splice_region_variant, intron_variant	Intron 3 of 15		NP_001269221.1
ABCB8	NM_001282293.2	c.300+4C>T		splice_region_variant, intron_variant	Intron 2 of 14		NP_001269222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB8	ENST00000358849.9	c.564+4C>T		splice_region_variant, intron_variant	Intron 3 of 15	1	NM_007188.5	ENSP00000351717.4

Frequencies

GnomAD3 genomes AF: 0.0160 AC: 2434 AN: 152162 Hom.: 42 Cov.: 33

Gnomad AFR AF: 0.0535

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00517

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00327

Gnomad SAS AF: 0.00538

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00107

Gnomad OTH AF: 0.0105

GnomAD2 exomes AF: 0.00545 AC: 1368 AN: 250954 AF XY: 0.00463

Gnomad AFR exome AF: 0.0541

Gnomad AMR exome AF: 0.00312

Gnomad ASJ exome AF: 0.000797

Gnomad EAS exome AF: 0.00348

Gnomad FIN exome AF: 0.000187

Gnomad NFE exome AF: 0.000863

Gnomad OTH exome AF: 0.00310

GnomAD4 exome AF: 0.00293 AC: 4278 AN: 1461592 Hom.: 65 Cov.: 35 AF XY: 0.00285 AC XY: 2075 AN XY: 727092

African (AFR) AF: 0.0569 AC: 1906 AN: 33480

American (AMR) AF: 0.00340 AC: 152 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.000460 AC: 12 AN: 26108

East Asian (EAS) AF: 0.00146 AC: 58 AN: 39700

South Asian (SAS) AF: 0.00585 AC: 505 AN: 86252

European-Finnish (FIN) AF: 0.000169 AC: 9 AN: 53224

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

European-Non Finnish (NFE) AF: 0.00118 AC: 1316 AN: 1111958

Other (OTH) AF: 0.00515 AC: 311 AN: 60388

GnomAD4 genome AF: 0.0160 AC: 2433 AN: 152280 Hom.: 42 Cov.: 33 AF XY: 0.0160 AC XY: 1188 AN XY: 74458

African (AFR) AF: 0.0533 AC: 2213 AN: 41532

American (AMR) AF: 0.00516 AC: 79 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3468

East Asian (EAS) AF: 0.00328 AC: 17 AN: 5182

South Asian (SAS) AF: 0.00539 AC: 26 AN: 4828

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10626

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

European-Non Finnish (NFE) AF: 0.00107 AC: 73 AN: 68022

Other (OTH) AF: 0.0104 AC: 22 AN: 2112

Alfa AF: 0.00583 Hom.: 25

Bravo AF: 0.0177

Asia WGS AF: 0.0120 AC: 41 AN: 3478

EpiCase AF: 0.00125

EpiControl AF: 0.000948

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Aug 08, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	8.6
DANN	Benign	0.73
PhyloP100		-0.14
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00025
dbscSNV1_RF	Benign	0.040
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: rs7776772; hg19: chr7-150731519;