rs7602204

Variant names:

• chr2-168986301-C-T
• rs7602204
• NM_003742.4:c.909-17G>A

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.909-17G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0345 in 1,606,816 control chromosomes in the GnomAD database, including 4,404 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (2247 hom., cov: 32)
  • Exomes 𝑓: 0.027 (2157 hom.)
• Consequence: ABCB11 NM_003742.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.635
• Publications: 1 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 2-168986301-C-T is Benign according to our data. Variant chr2-168986301-C-T is described in ClinVar as Benign. ClinVar VariationId is 259159.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.316 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.909-17G>A		intron	N/A	NP_003733.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB11	ENST00000650372.1	MANE Select	c.909-17G>A		intron	N/A	ENSP00000497931.1	O95342
	ABCB11	ENST00000858973.1		c.951-17G>A		intron	N/A	ENSP00000529032.1
	ABCB11	ENST00000858972.1		c.909-17G>A		intron	N/A	ENSP00000529031.1

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15976 AN: 151964 Hom.: 2236 Cov.: 32

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0515

Gnomad ASJ AF: 0.0262

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.0315

Gnomad FIN AF: 0.00358

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0215

Gnomad OTH AF: 0.0852

GnomAD2 exomes AF: 0.0391 AC: 9662 AN: 247360 AF XY: 0.0346

Gnomad AFR exome AF: 0.327

Gnomad AMR exome AF: 0.0269

Gnomad ASJ exome AF: 0.0257

Gnomad EAS exome AF: 0.000613

Gnomad FIN exome AF: 0.00343

Gnomad NFE exome AF: 0.0203

Gnomad OTH exome AF: 0.0297

GnomAD4 exome AF: 0.0271 AC: 39372 AN: 1454734 Hom.: 2157 Cov.: 29 AF XY: 0.0262 AC XY: 18963 AN XY: 723928

African (AFR) AF: 0.325 AC: 10717 AN: 33026

American (AMR) AF: 0.0301 AC: 1339 AN: 44540

Ashkenazi Jewish (ASJ) AF: 0.0267 AC: 695 AN: 26028

East Asian (EAS) AF: 0.000328 AC: 13 AN: 39652

South Asian (SAS) AF: 0.0299 AC: 2568 AN: 85896

European-Finnish (FIN) AF: 0.00393 AC: 209 AN: 53200

Middle Eastern (MID) AF: 0.0519 AC: 232 AN: 4474

European-Non Finnish (NFE) AF: 0.0192 AC: 21266 AN: 1107904

Other (OTH) AF: 0.0389 AC: 2333 AN: 60014

GnomAD4 genome AF: 0.105 AC: 16024 AN: 152082 Hom.: 2247 Cov.: 32 AF XY: 0.101 AC XY: 7539 AN XY: 74346

African (AFR) AF: 0.321 AC: 13301 AN: 41444

American (AMR) AF: 0.0514 AC: 785 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0262 AC: 91 AN: 3470

East Asian (EAS) AF: 0.000581 AC: 3 AN: 5162

South Asian (SAS) AF: 0.0309 AC: 149 AN: 4822

European-Finnish (FIN) AF: 0.00358 AC: 38 AN: 10606

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

European-Non Finnish (NFE) AF: 0.0215 AC: 1465 AN: 67990

Other (OTH) AF: 0.0848 AC: 179 AN: 2112

Alfa AF: 0.0631 Hom.: 196

Bravo AF: 0.118

Asia WGS AF: 0.0390 AC: 135 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.49
PhyloP100		0.64
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: rs7602204; hg19: chr2-169842811;