1-229530290-C-T

Variant names:

• chr1-229530290-C-T
• rs140426197
• NM_012089.3:c.1554G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_012089.3(ABCB10):​c.1554G>A​(p.Pro518Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00483 in 1,614,040 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0030 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0050 (30 hom.)
• Consequence: ABCB10 NM_012089.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.519
• Publications: 4 publications found

Genes affected

ABCB10 (HGNC:41): (ATP binding cassette subfamily B member 10) The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance. The function of this mitochondrial protein is unknown. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 1-229530290-C-T is Benign according to our data. Variant chr1-229530290-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2640063.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.519 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 30 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012089.3. 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
	ABCB10	NM_012089.3	MANE Select	c.1554G>A	p.Pro518Pro	synonymous	Exon 8 of 13	NP_036221.2	Q9NRK6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB10	ENST00000344517.5	TSL:1 MANE Select	c.1554G>A	p.Pro518Pro	synonymous	Exon 8 of 13	ENSP00000355637.3	Q9NRK6
	ABCB10	ENST00000946247.1		c.1605G>A	p.Pro535Pro	synonymous	Exon 8 of 13	ENSP00000616306.1
	ABCB10	ENST00000946244.1		c.1554G>A	p.Pro518Pro	synonymous	Exon 8 of 12	ENSP00000616303.1

Frequencies

GnomAD3 genomes AF: 0.00298 AC: 453 AN: 152030 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000991

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00321

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00642

Gnomad FIN AF: 0.000852

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00441

Gnomad OTH AF: 0.00288

GnomAD2 exomes AF: 0.00383 AC: 962 AN: 251474 AF XY: 0.00424

Gnomad AFR exome AF: 0.000923

Gnomad AMR exome AF: 0.00150

Gnomad ASJ exome AF: 0.00585

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00115

Gnomad NFE exome AF: 0.00486

Gnomad OTH exome AF: 0.00440

GnomAD4 exome AF: 0.00503 AC: 7347 AN: 1461892 Hom.: 30 Cov.: 31 AF XY: 0.00515 AC XY: 3745 AN XY: 727248

African (AFR) AF: 0.000777 AC: 26 AN: 33480

American (AMR) AF: 0.00139 AC: 62 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00517 AC: 135 AN: 26136

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39700

South Asian (SAS) AF: 0.00809 AC: 698 AN: 86258

European-Finnish (FIN) AF: 0.000992 AC: 53 AN: 53420

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

European-Non Finnish (NFE) AF: 0.00546 AC: 6070 AN: 1112010

Other (OTH) AF: 0.00480 AC: 290 AN: 60396

GnomAD4 genome AF: 0.00298 AC: 454 AN: 152148 Hom.: 1 Cov.: 32 AF XY: 0.00265 AC XY: 197 AN XY: 74362

African (AFR) AF: 0.000988 AC: 41 AN: 41502

American (AMR) AF: 0.00321 AC: 49 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00490 AC: 17 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00663 AC: 32 AN: 4824

European-Finnish (FIN) AF: 0.000852 AC: 9 AN: 10558

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

European-Non Finnish (NFE) AF: 0.00441 AC: 300 AN: 68020

Other (OTH) AF: 0.00285 AC: 6 AN: 2108

Alfa AF: 0.00365 Hom.: 3

Bravo AF: 0.00325

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.00502

EpiControl AF: 0.00415

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	7.2
DANN	Benign	0.85
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs140426197; hg19: chr1-229666037; COSMIC: COSV60621872; COSMIC: COSV60621872;