rs2241133

Variant names:

• chr2-201642630-G-C
• rs2241133
• ENST00000621467.5:c.-409C>G

Your query was ambiguous. Multiple possible variants found:

• chr2-201642630-G-C
• chr2-201642630-G-A
• chr2-201642630-G-T

Variant summary

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

The NM_152388.4(TMEM237):​c.-4C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0327 in 1,608,188 control chromosomes in the GnomAD database, including 3,101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.074 (876 hom., cov: 32)
  • Exomes 𝑓: 0.028 (2225 hom.)
• Consequence: TMEM237 NM_152388.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.139
• Publications: 7 publications found

Genes affected

TMEM237 (HGNC:14432): (transmembrane protein 237) The protein encoded by this gene is a tetraspanin protein that is thought to be involved in WNT signaling. Defects in this gene are a cause of Joubert syndrome-14. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

TMEM237 Gene-Disease associations (from GenCC):

• Joubert syndrome 14

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, PanelApp Australia, ClinGen, Labcorp Genetics (formerly Invitae)
• Joubert syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Joubert syndrome with oculorenal defect

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Joubert syndrome with renal defect

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Meckel syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 2-201642630-G-C is Benign according to our data. Variant chr2-201642630-G-C is described in ClinVar as Benign. ClinVar VariationId is 137672.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152388.4. 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
	TMEM237	NM_001044385.3	MANE Select	c.42+729C>G		intron	N/A	NP_001037850.1	Q96Q45-1
	TMEM237	NM_152388.4		c.-4C>G		5_prime_UTR	Exon 1 of 13	NP_689601.2	Q96Q45-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM237	ENST00000621467.5	TSL:1	c.-409C>G		5_prime_UTR	Exon 1 of 13	ENSP00000480508.2	A0A087WWU1
	TMEM237	ENST00000409883.7	TSL:5 MANE Select	c.42+729C>G		intron	N/A	ENSP00000386264.2	Q96Q45-1
	TMEM237	ENST00000409444.6	TSL:5	c.-4C>G		5_prime_UTR	Exon 1 of 13	ENSP00000387203.2	Q96Q45-2

Frequencies

GnomAD3 genomes AF: 0.0742 AC: 11297 AN: 152186 Hom.: 873 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0302

Gnomad ASJ AF: 0.0219

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.0478

Gnomad FIN AF: 0.0514

Gnomad MID AF: 0.0223

Gnomad NFE AF: 0.0156

Gnomad OTH AF: 0.0540

GnomAD2 exomes AF: 0.0473 AC: 11381 AN: 240368 AF XY: 0.0445

Gnomad AFR exome AF: 0.172

Gnomad AMR exome AF: 0.0164

Gnomad ASJ exome AF: 0.0190

Gnomad EAS exome AF: 0.232

Gnomad FIN exome AF: 0.0495

Gnomad NFE exome AF: 0.0173

Gnomad OTH exome AF: 0.0343

GnomAD4 exome AF: 0.0284 AC: 41298 AN: 1455884 Hom.: 2225 Cov.: 31 AF XY: 0.0279 AC XY: 20188 AN XY: 724416

African (AFR) AF: 0.180 AC: 5886 AN: 32652

American (AMR) AF: 0.0176 AC: 766 AN: 43596

Ashkenazi Jewish (ASJ) AF: 0.0206 AC: 535 AN: 25990

East Asian (EAS) AF: 0.256 AC: 9901 AN: 38654

South Asian (SAS) AF: 0.0376 AC: 3216 AN: 85554

European-Finnish (FIN) AF: 0.0462 AC: 2452 AN: 53074

Middle Eastern (MID) AF: 0.0269 AC: 155 AN: 5756

European-Non Finnish (NFE) AF: 0.0143 AC: 15895 AN: 1110544

Other (OTH) AF: 0.0415 AC: 2492 AN: 60064

GnomAD4 genome AF: 0.0742 AC: 11306 AN: 152304 Hom.: 876 Cov.: 32 AF XY: 0.0761 AC XY: 5671 AN XY: 74482

African (AFR) AF: 0.184 AC: 7640 AN: 41560

American (AMR) AF: 0.0302 AC: 462 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0219 AC: 76 AN: 3472

East Asian (EAS) AF: 0.224 AC: 1161 AN: 5172

South Asian (SAS) AF: 0.0472 AC: 228 AN: 4832

European-Finnish (FIN) AF: 0.0514 AC: 545 AN: 10610

Middle Eastern (MID) AF: 0.0171 AC: 5 AN: 292

European-Non Finnish (NFE) AF: 0.0156 AC: 1062 AN: 68032

Other (OTH) AF: 0.0582 AC: 123 AN: 2114

Alfa AF: 0.0309 Hom.: 81

Bravo AF: 0.0772

Asia WGS AF: 0.133 AC: 461 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.1
DANN	Benign	0.57
PhyloP100		0.14
PromoterAI		0.042	Neutral
Mutation Taster		=300/0	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: rs2241133; hg19: chr2-202507353; COSMIC: COSV53805410; COSMIC: COSV53805410;