2-168923386-T-C

Variant names:

• chr2-168923386-T-C
• rs473351
• NM_003742.4:c.*236A>G

Variant summary

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

The NM_003742.4(ABCB11):​c.*236A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 570,900 control chromosomes in the GnomAD database, including 112,586 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.62 (30228 hom., cov: 30)
  • Exomes 𝑓: 0.62 (82358 hom.)
• Consequence: ABCB11 NM_003742.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.225
• Publications: 21 publications found

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]

ABCB11 Gene-Disease associations (from GenCC):

• progressive familial intrahepatic cholestasis type 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)
• benign recurrent intrahepatic cholestasis type 2

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 2-168923386-T-C is Benign according to our data. Variant chr2-168923386-T-C is described in ClinVar as Benign. ClinVar VariationId is 332018.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003742.4. 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
	ABCB11	NM_003742.4	MANE Select	c.*236A>G		3_prime_UTR	Exon 28 of 28	NP_003733.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB11	ENST00000650372.1	MANE Select	c.*236A>G		3_prime_UTR	Exon 28 of 28	ENSP00000497931.1	O95342
	ABCB11	ENST00000858973.1		c.*236A>G		3_prime_UTR	Exon 28 of 28	ENSP00000529032.1
	ABCB11	ENST00000858972.1		c.*236A>G		3_prime_UTR	Exon 27 of 27	ENSP00000529031.1

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94766 AN: 151856 Hom.: 30197 Cov.: 30

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.761

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.651

Gnomad EAS AF: 0.927

Gnomad SAS AF: 0.772

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.619

GnomAD4 exome AF: 0.616 AC: 257905 AN: 418926 Hom.: 82358 Cov.: 4 AF XY: 0.623 AC XY: 137126 AN XY: 220164

African (AFR) AF: 0.683 AC: 8176 AN: 11964

American (AMR) AF: 0.648 AC: 11108 AN: 17142

Ashkenazi Jewish (ASJ) AF: 0.656 AC: 8488 AN: 12938

East Asian (EAS) AF: 0.940 AC: 27440 AN: 29180

South Asian (SAS) AF: 0.764 AC: 30113 AN: 39426

European-Finnish (FIN) AF: 0.598 AC: 16096 AN: 26934

Middle Eastern (MID) AF: 0.594 AC: 1114 AN: 1874

European-Non Finnish (NFE) AF: 0.550 AC: 140343 AN: 255058

Other (OTH) AF: 0.616 AC: 15027 AN: 24410

GnomAD4 genome AF: 0.624 AC: 94858 AN: 151974 Hom.: 30228 Cov.: 30 AF XY: 0.633 AC XY: 47025 AN XY: 74282

African (AFR) AF: 0.681 AC: 28236 AN: 41440

American (AMR) AF: 0.629 AC: 9612 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.651 AC: 2256 AN: 3466

East Asian (EAS) AF: 0.927 AC: 4787 AN: 5166

South Asian (SAS) AF: 0.771 AC: 3697 AN: 4794

European-Finnish (FIN) AF: 0.611 AC: 6463 AN: 10572

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.554 AC: 37633 AN: 67938

Other (OTH) AF: 0.616 AC: 1300 AN: 2112

Alfa AF: 0.578 Hom.: 67955

Bravo AF: 0.624

Asia WGS AF: 0.803 AC: 2792 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Progressive familial intrahepatic cholestasis type 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.7
DANN	Benign	0.61
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism (auto)

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: rs473351; hg19: chr2-169779896;