rs7104819

Variant names:

• chr11-118898733-A-G
• rs7104819
• NM_001378213.1:c.4182T>C

Variant summary

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

The NM_001378213.1(BCL9L):​c.4182T>C​(p.Pro1394Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 1,612,734 control chromosomes in the GnomAD database, including 144,976 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (18730 hom., cov: 34)
  • Exomes 𝑓: 0.41 (126246 hom.)
• Consequence: BCL9L NM_001378213.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.65
• Publications: 21 publications found

Genes affected

BCL9L (HGNC:23688): (BCL9 like) Enables beta-catenin binding activity. Involved in several processes, including negative regulation of transforming growth factor beta receptor signaling pathway; positive regulation of epithelial to mesenchymal transition; and positive regulation of transcription by RNA polymerase II. Located in nucleolus and nucleoplasm. Part of beta-catenin-TCF complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 11-118898733-A-G is Benign according to our data. Variant chr11-118898733-A-G is described in ClinVar as Benign. ClinVar VariationId is 402412.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.65 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378213.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL9L	NM_001378213.1	MANE Select	c.4182T>C	p.Pro1394Pro	synonymous	Exon 10 of 10	NP_001365142.1
	BCL9L	NM_182557.4		c.4182T>C	p.Pro1394Pro	synonymous	Exon 8 of 8	NP_872363.1
	BCL9L	NM_001378214.1		c.4071T>C	p.Pro1357Pro	synonymous	Exon 9 of 9	NP_001365143.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL9L	ENST00000683865.1	MANE Select	c.4182T>C	p.Pro1394Pro	synonymous	Exon 10 of 10	ENSP00000507778.1
	BCL9L	ENST00000334801.7	TSL:1	c.4182T>C	p.Pro1394Pro	synonymous	Exon 8 of 8	ENSP00000335320.3
	BCL9L	ENST00000526143.2	TSL:5	c.4071T>C	p.Pro1357Pro	synonymous	Exon 8 of 8	ENSP00000482938.1

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73359 AN: 152028 Hom.: 18679 Cov.: 34

Gnomad AFR AF: 0.638

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.468

GnomAD2 exomes AF: 0.428 AC: 105778 AN: 247098 AF XY: 0.414

Gnomad AFR exome AF: 0.635

Gnomad AMR exome AF: 0.580

Gnomad ASJ exome AF: 0.434

Gnomad EAS exome AF: 0.318

Gnomad FIN exome AF: 0.428

Gnomad NFE exome AF: 0.411

Gnomad OTH exome AF: 0.425

GnomAD4 exome AF: 0.410 AC: 599451 AN: 1460588 Hom.: 126246 Cov.: 81 AF XY: 0.406 AC XY: 295129 AN XY: 726546

African (AFR) AF: 0.644 AC: 21541 AN: 33468

American (AMR) AF: 0.577 AC: 25730 AN: 44556

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 11484 AN: 26112

East Asian (EAS) AF: 0.257 AC: 10186 AN: 39682

South Asian (SAS) AF: 0.280 AC: 24133 AN: 86192

European-Finnish (FIN) AF: 0.424 AC: 22409 AN: 52828

Middle Eastern (MID) AF: 0.468 AC: 2693 AN: 5760

European-Non Finnish (NFE) AF: 0.410 AC: 455468 AN: 1111630

Other (OTH) AF: 0.428 AC: 25807 AN: 60360

GnomAD4 genome AF: 0.483 AC: 73456 AN: 152146 Hom.: 18730 Cov.: 34 AF XY: 0.481 AC XY: 35814 AN XY: 74394

African (AFR) AF: 0.639 AC: 26507 AN: 41506

American (AMR) AF: 0.548 AC: 8384 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 1534 AN: 3468

East Asian (EAS) AF: 0.303 AC: 1567 AN: 5168

South Asian (SAS) AF: 0.251 AC: 1211 AN: 4824

European-Finnish (FIN) AF: 0.437 AC: 4633 AN: 10604

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.415 AC: 28180 AN: 67956

Other (OTH) AF: 0.465 AC: 983 AN: 2116

Alfa AF: 0.435 Hom.: 5196

Bravo AF: 0.501

Asia WGS AF: 0.289 AC: 1004 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.3
DANN	Benign	0.59
PhyloP100		-1.6
Mutation Taster		=99/1	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: rs7104819; hg19: chr11-118769442; COSMIC: COSV52682971; COSMIC: COSV52682971;