2-168958145-G-T

Variant names:

• chr2-168958145-G-T
• rs853772
• NM_003742.4:c.2179-17C>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.2179-17C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 1,605,162 control chromosomes in the GnomAD database, including 226,548 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (17710 hom., cov: 31)
  • Exomes 𝑓: 0.53 (208838 hom.)
• Consequence: ABCB11 NM_003742.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.0820
• 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: 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=-0.83).
• BP6: Variant 2-168958145-G-T is Benign according to our data. Variant chr2-168958145-G-T is described in ClinVar as Benign. ClinVar VariationId is 259147.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.632 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.2179-17C>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.2179-17C>A		intron	N/A	ENSP00000497931.1
	ABCB11	ENST00000858973.1		c.2221-17C>A		intron	N/A	ENSP00000529032.1
	ABCB11	ENST00000858972.1		c.2179-17C>A		intron	N/A	ENSP00000529031.1

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70467 AN: 151290 Hom.: 17717 Cov.: 31

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.730

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.652

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.495

GnomAD2 exomes AF: 0.547 AC: 133904 AN: 244912 AF XY: 0.553

Gnomad AFR exome AF: 0.265

Gnomad AMR exome AF: 0.597

Gnomad ASJ exome AF: 0.605

Gnomad EAS exome AF: 0.636

Gnomad FIN exome AF: 0.527

Gnomad NFE exome AF: 0.526

Gnomad OTH exome AF: 0.535

GnomAD4 exome AF: 0.532 AC: 774065 AN: 1453754 Hom.: 208838 Cov.: 32 AF XY: 0.537 AC XY: 388425 AN XY: 723142

African (AFR) AF: 0.264 AC: 8755 AN: 33220

American (AMR) AF: 0.583 AC: 25969 AN: 44512

Ashkenazi Jewish (ASJ) AF: 0.605 AC: 15678 AN: 25932

East Asian (EAS) AF: 0.612 AC: 24210 AN: 39576

South Asian (SAS) AF: 0.653 AC: 56085 AN: 85944

European-Finnish (FIN) AF: 0.522 AC: 27480 AN: 52636

Middle Eastern (MID) AF: 0.565 AC: 3145 AN: 5562

European-Non Finnish (NFE) AF: 0.525 AC: 580707 AN: 1106370

Other (OTH) AF: 0.534 AC: 32036 AN: 60002

GnomAD4 genome AF: 0.465 AC: 70479 AN: 151408 Hom.: 17710 Cov.: 31 AF XY: 0.473 AC XY: 34984 AN XY: 73942

African (AFR) AF: 0.272 AC: 11252 AN: 41388

American (AMR) AF: 0.518 AC: 7877 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.592 AC: 2045 AN: 3456

East Asian (EAS) AF: 0.640 AC: 3257 AN: 5088

South Asian (SAS) AF: 0.651 AC: 3136 AN: 4820

European-Finnish (FIN) AF: 0.537 AC: 5659 AN: 10532

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.524 AC: 35408 AN: 67626

Other (OTH) AF: 0.489 AC: 1026 AN: 2098

Alfa AF: 0.510 Hom.: 36046

Bravo AF: 0.453

Asia WGS AF: 0.605 AC: 2102 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	not provided (2)
-	-	1	Benign recurrent intrahepatic cholestasis type 2 (1)
-	-	1	Progressive familial intrahepatic cholestasis type 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.4
DANN	Benign	0.58
PhyloP100		0.082
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs853772; hg19: chr2-169814655;