rs7563233

Variant names:

• chr2-168986236-T-C
• rs7563233
• NM_003742.4:c.957A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-168986236-T-C
• chr2-168986236-T-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_003742.4(ABCB11):​c.957A>G​(p.Gly319Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0347 in 1,613,030 control chromosomes in the GnomAD database, including 4,449 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (2254 hom., cov: 32)
  • Exomes 𝑓: 0.027 (2195 hom.)
• Consequence: ABCB11 NM_003742.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.967
• Publications: 16 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: G2P, Orphanet, 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 2-168986236-T-C is Benign according to our data. Variant chr2-168986236-T-C is described in ClinVar as Benign. ClinVar VariationId is 193662.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.967 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.317 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.957A>G	p.Gly319Gly	synonymous	Exon 10 of 28	NP_003733.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB11	ENST00000650372.1	MANE Select	c.957A>G	p.Gly319Gly	synonymous	Exon 10 of 28	ENSP00000497931.1	O95342
	ABCB11	ENST00000858973.1		c.999A>G	p.Gly333Gly	synonymous	Exon 10 of 28	ENSP00000529032.1
	ABCB11	ENST00000858972.1		c.957A>G	p.Gly319Gly	synonymous	Exon 10 of 27	ENSP00000529031.1

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15982 AN: 151940 Hom.: 2243 Cov.: 32

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0514

Gnomad ASJ AF: 0.0262

Gnomad EAS AF: 0.000581

Gnomad SAS AF: 0.0317

Gnomad FIN AF: 0.00358

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0215

Gnomad OTH AF: 0.0844

GnomAD2 exomes AF: 0.0392 AC: 9743 AN: 248786 AF XY: 0.0347

Gnomad AFR exome AF: 0.327

Gnomad AMR exome AF: 0.0270

Gnomad ASJ exome AF: 0.0261

Gnomad EAS exome AF: 0.000613

Gnomad FIN exome AF: 0.00353

Gnomad NFE exome AF: 0.0204

Gnomad OTH exome AF: 0.0298

GnomAD4 exome AF: 0.0273 AC: 39947 AN: 1460972 Hom.: 2195 Cov.: 31 AF XY: 0.0264 AC XY: 19215 AN XY: 726778

African (AFR) AF: 0.326 AC: 10902 AN: 33422

American (AMR) AF: 0.0302 AC: 1348 AN: 44646

Ashkenazi Jewish (ASJ) AF: 0.0270 AC: 704 AN: 26122

East Asian (EAS) AF: 0.000328 AC: 13 AN: 39684

South Asian (SAS) AF: 0.0301 AC: 2592 AN: 86232

European-Finnish (FIN) AF: 0.00395 AC: 211 AN: 53394

Middle Eastern (MID) AF: 0.0502 AC: 283 AN: 5636

European-Non Finnish (NFE) AF: 0.0194 AC: 21524 AN: 1111510

Other (OTH) AF: 0.0393 AC: 2370 AN: 60326

GnomAD4 genome AF: 0.105 AC: 16030 AN: 152058 Hom.: 2254 Cov.: 32 AF XY: 0.101 AC XY: 7539 AN XY: 74350

African (AFR) AF: 0.321 AC: 13309 AN: 41414

American (AMR) AF: 0.0514 AC: 784 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0262 AC: 91 AN: 3468

East Asian (EAS) AF: 0.000583 AC: 3 AN: 5150

South Asian (SAS) AF: 0.0311 AC: 150 AN: 4818

European-Finnish (FIN) AF: 0.00358 AC: 38 AN: 10618

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0215 AC: 1465 AN: 68012

Other (OTH) AF: 0.0840 AC: 177 AN: 2108

Alfa AF: 0.0420 Hom.: 2172

Bravo AF: 0.118

Asia WGS AF: 0.0390 AC: 135 AN: 3478

EpiCase AF: 0.0241

EpiControl AF: 0.0244

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	2	Progressive familial intrahepatic cholestasis type 2 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.0
DANN	Benign	0.59
PhyloP100		-0.97
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs7563233; hg19: chr2-169842746;