chr2-168935661-C-T

Position:

• chr2-168935661-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003742.4(ABCB11):​c.2815-236G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,008 control chromosomes in the GnomAD database, including 2,740 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.17 (2740 hom., cov: 32)
• Consequence: ABCB11 NM_003742.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.27

Genes affected

ABCB11 (HGNC:42): (ATP binding cassette subfamily B member 11) 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 protein encoded by this gene is the major canalicular bile salt export pump in man. Mutations in this gene cause a form of progressive familial intrahepatic cholestases which are a group of inherited disorders with severe cholestatic liver disease from early infancy. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 2-168935661-C-T is Benign according to our data. Variant chr2-168935661-C-T is described in ClinVar as [Benign]. Clinvar id is 1241955.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCB11	NM_003742.4	c.2815-236G>A		intron_variant		ENST00000650372.1	NP_003733.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCB11	ENST00000650372.1	c.2815-236G>A		intron_variant			NM_003742.4	ENSP00000497931.1
ABCB11	ENST00000649448.1	c.1132-236G>A		intron_variant				ENSP00000497165.1
ABCB11	ENST00000439188.1	n.*1285-236G>A		intron_variant		2		ENSP00000416058.1

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25994 AN: 151888 Hom.: 2734 Cov.: 32

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.156

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.171 AC: 26041 AN: 152008 Hom.: 2740 Cov.: 32 AF XY: 0.172 AC XY: 12782 AN XY: 74288

Gnomad4 AFR AF: 0.279

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.321

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.160

Alfa AF: 0.119 Hom.: 1202

Bravo AF: 0.186

Asia WGS AF: 0.216 AC: 750 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.8
DANN	Benign	0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs3755157; hg19: chr2-169792171;