rs2854344

Variant names:

• chr13-48423557-G-A
• rs2854344
• NM_000321.3:c.1696-29436G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-48423557-G-A
• chr13-48423557-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000321.3(RB1):​c.1696-29436G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0409 in 152,146 control chromosomes in the GnomAD database, including 200 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.041 (200 hom., cov: 32)
• Consequence: RB1 NM_000321.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.389
• Publications: 34 publications found

Genes affected

RB1 (HGNC:9884): (RB transcriptional corepressor 1) The protein encoded by this gene is a negative regulator of the cell cycle and was the first tumor suppressor gene found. The encoded protein also stabilizes constitutive heterochromatin to maintain the overall chromatin structure. The active, hypophosphorylated form of the protein binds transcription factor E2F1. Defects in this gene are a cause of childhood cancer retinoblastoma (RB), bladder cancer, and osteogenic sarcoma. [provided by RefSeq, Jul 2008]

LPAR6 (HGNC:15520): (lysophosphatidic acid receptor 6) The protein encoded by this gene belongs to the family of G-protein coupled receptors, that are preferentially activated by adenosine and uridine nucleotides. This gene aligns with an internal intron of the retinoblastoma susceptibility gene in the reverse orientation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2009]

LPAR6 Gene-Disease associations (from GenCC):

• hypotrichosis 8

  Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• hypotrichosis simplex

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• isolated familial wooly hair disorder

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0635 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000321.3. 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
	RB1	NM_000321.3	MANE Select	c.1696-29436G>A		intron	N/A	NP_000312.2	P06400
	RB1	NM_001407165.1		c.1696-29436G>A		intron	N/A	NP_001394094.1	A0A3B3IS71
	LPAR6	NM_001162497.3		c.-1094-767C>T		intron	N/A	NP_001155969.1	P43657

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RB1	ENST00000267163.6	TSL:1 MANE Select	c.1696-29436G>A		intron	N/A	ENSP00000267163.4	P06400
	LPAR6	ENST00000378434.8	TSL:1	c.-1347+436C>T		intron	N/A	ENSP00000367691.3	P43657
	LPAR6	ENST00000465365.6	TSL:1	n.662+436C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0409 AC: 6218 AN: 152028 Hom.: 200 Cov.: 32

Gnomad AFR AF: 0.0110

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.0354

Gnomad ASJ AF: 0.0236

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00373

Gnomad FIN AF: 0.0453

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0651

Gnomad OTH AF: 0.0398

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0409 AC: 6217 AN: 152146 Hom.: 200 Cov.: 32 AF XY: 0.0387 AC XY: 2880 AN XY: 74378

African (AFR) AF: 0.0110 AC: 457 AN: 41498

American (AMR) AF: 0.0353 AC: 539 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0236 AC: 82 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00373 AC: 18 AN: 4824

European-Finnish (FIN) AF: 0.0453 AC: 479 AN: 10566

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0651 AC: 4426 AN: 68006

Other (OTH) AF: 0.0393 AC: 83 AN: 2110

Alfa AF: 0.0550 Hom.: 443

Bravo AF: 0.0398

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.71
DANN	Benign	0.60
PhyloP100		-0.39
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: rs2854344; hg19: chr13-48997693;