rs31668

Variant names:

• chr7-87423890-G-A
• rs31668
• NM_000443.4:c.2211+16C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-87423890-G-A
• chr7-87423890-G-T
• chr7-87423890-G-C

Variant summary

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

The NM_000443.4(ABCB4):​c.2211+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.916 in 1,613,788 control chromosomes in the GnomAD database, including 678,063 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.92 (64300 hom., cov: 31)
  • Exomes 𝑓: 0.92 (613763 hom.)
• Consequence: ABCB4 NM_000443.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -1.67
• Publications: 14 publications found

Genes affected

ABCB4 (HGNC:45): (ATP binding cassette subfamily B member 4) 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 as well as antigen presentation. This gene encodes a full transporter and member of the p-glycoprotein family of membrane proteins with phosphatidylcholine as its substrate. The function of this protein has not yet been determined; however, it may involve transport of phospholipids from liver hepatocytes into bile. Alternative splicing of this gene results in several products of undetermined function. [provided by RefSeq, Jul 2008]

ABCB4 Gene-Disease associations (from GenCC):

• progressive familial intrahepatic cholestasis type 3

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen
• gallbladder disease 1

  Inheritance: SD, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• pancreatitis

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 7-87423890-G-A is Benign according to our data. Variant chr7-87423890-G-A is described in ClinVar as Benign. ClinVar VariationId is 256161.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000443.4. 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
	ABCB4	NM_000443.4	MANE Select	c.2211+16C>T		intron	N/A	NP_000434.1	P21439-2
	ABCB4	NM_018849.3		c.2211+16C>T		intron	N/A	NP_061337.1	P21439-1
	ABCB4	NM_018850.3		c.2211+16C>T		intron	N/A	NP_061338.1	P21439-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB4	ENST00000649586.2	MANE Select	c.2211+16C>T		intron	N/A	ENSP00000496956.2	P21439-2
	ABCB4	ENST00000265723.8	TSL:1	c.2211+16C>T		intron	N/A	ENSP00000265723.4	P21439-1
	ABCB4	ENST00000359206.8	TSL:1	c.2211+16C>T		intron	N/A	ENSP00000352135.3	P21439-2

Frequencies

GnomAD3 genomes AF: 0.918 AC: 139627 AN: 152096 Hom.: 64255 Cov.: 31

Gnomad AFR AF: 0.933

Gnomad AMI AF: 0.979

Gnomad AMR AF: 0.927

Gnomad ASJ AF: 0.901

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.889

Gnomad FIN AF: 0.936

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.922

Gnomad OTH AF: 0.921

GnomAD2 exomes AF: 0.897 AC: 225437 AN: 251260 AF XY: 0.898

Gnomad AFR exome AF: 0.936

Gnomad AMR exome AF: 0.878

Gnomad ASJ exome AF: 0.896

Gnomad EAS exome AF: 0.706

Gnomad FIN exome AF: 0.926

Gnomad NFE exome AF: 0.925

Gnomad OTH exome AF: 0.911

GnomAD4 exome AF: 0.915 AC: 1337974 AN: 1461574 Hom.: 613763 Cov.: 48 AF XY: 0.915 AC XY: 665006 AN XY: 727096

African (AFR) AF: 0.939 AC: 31418 AN: 33468

American (AMR) AF: 0.883 AC: 39498 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.896 AC: 23399 AN: 26126

East Asian (EAS) AF: 0.705 AC: 27977 AN: 39688

South Asian (SAS) AF: 0.889 AC: 76684 AN: 86256

European-Finnish (FIN) AF: 0.928 AC: 49579 AN: 53410

Middle Eastern (MID) AF: 0.921 AC: 5310 AN: 5764

European-Non Finnish (NFE) AF: 0.926 AC: 1029432 AN: 1111760

Other (OTH) AF: 0.906 AC: 54677 AN: 60380

GnomAD4 genome AF: 0.918 AC: 139728 AN: 152214 Hom.: 64300 Cov.: 31 AF XY: 0.919 AC XY: 68343 AN XY: 74406

African (AFR) AF: 0.933 AC: 38762 AN: 41546

American (AMR) AF: 0.926 AC: 14160 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.901 AC: 3130 AN: 3472

East Asian (EAS) AF: 0.709 AC: 3665 AN: 5168

South Asian (SAS) AF: 0.888 AC: 4277 AN: 4814

European-Finnish (FIN) AF: 0.936 AC: 9919 AN: 10596

Middle Eastern (MID) AF: 0.939 AC: 276 AN: 294

European-Non Finnish (NFE) AF: 0.922 AC: 62706 AN: 68014

Other (OTH) AF: 0.918 AC: 1940 AN: 2114

Alfa AF: 0.920 Hom.: 111577

Bravo AF: 0.915

Asia WGS AF: 0.820 AC: 2850 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	2	not provided (2)
-	-	1	Cholestasis, intrahepatic, of pregnancy, 3 (1)
-	-	1	Progressive familial intrahepatic cholestasis type 3 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.55
DANN	Benign	0.49
PhyloP100		-1.7
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: rs31668; hg19: chr7-87053206; COSMIC: COSV55935714; COSMIC: COSV55935714;