1-109274968-G-T

Variant names:

• chr1-109274968-G-T
• rs12740374
• NM_001408.3:c.*919G>T

Variant summary

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

The NM_001408.3(CELSR2):​c.*919G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 152,454 control chromosomes in the GnomAD database, including 3,965 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency:
  • Genomes: 𝑓 0.22 (3957 hom., cov: 32)
  • Exomes 𝑓: 0.19 (8 hom.)
• Consequence: CELSR2 NM_001408.3 3_prime_UTR
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -0.174
• Publications: 312 publications found

Genes affected

CELSR2 (HGNC:3231): (cadherin EGF LAG seven-pass G-type receptor 2) The protein encoded by this gene is a member of the flamingo subfamily, part of the cadherin superfamily. The flamingo subfamily consists of nonclassic-type cadherins; a subpopulation that does not interact with catenins. The flamingo cadherins are located at the plasma membrane and have nine cadherin domains, seven epidermal growth factor-like repeats and two laminin A G-type repeats in their ectodomain. They also have seven transmembrane domains, a characteristic unique to this subfamily. It is postulated that these proteins are receptors involved in contact-mediated communication, with cadherin domains acting as homophilic binding regions and the EGF-like domains involved in cell adhesion and receptor-ligand interactions. The specific function of this particular member has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001408.3. 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
	CELSR2	NM_001408.3	MANE Select	c.*919G>T		3_prime_UTR	Exon 34 of 34	NP_001399.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELSR2	ENST00000271332.4	TSL:1 MANE Select	c.*919G>T		3_prime_UTR	Exon 34 of 34	ENSP00000271332.3
	CELSR2	ENST00000498157.1	TSL:2	n.3041G>T		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33705 AN: 151890 Hom.: 3948 Cov.: 32

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.0623

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.214

GnomAD4 exome AF: 0.187 AC: 83 AN: 444 Hom.: 8 Cov.: 0 AF XY: 0.199 AC XY: 55 AN XY: 276

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.197 AC: 77 AN: 390

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.104 AC: 5 AN: 48

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.222 AC: 33745 AN: 152010 Hom.: 3957 Cov.: 32 AF XY: 0.223 AC XY: 16573 AN XY: 74328

African (AFR) AF: 0.249 AC: 10334 AN: 41442

American (AMR) AF: 0.210 AC: 3213 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 586 AN: 3468

East Asian (EAS) AF: 0.0620 AC: 320 AN: 5162

South Asian (SAS) AF: 0.244 AC: 1176 AN: 4820

European-Finnish (FIN) AF: 0.221 AC: 2336 AN: 10568

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.221 AC: 15001 AN: 67940

Other (OTH) AF: 0.212 AC: 449 AN: 2114

Alfa AF: 0.216 Hom.: 12832

Bravo AF: 0.222

Asia WGS AF: 0.152 AC: 528 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: association

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	LOW DENSITY LIPOPROTEIN CHOLESTEROL LEVEL QUANTITATIVE TRAIT LOCUS 6 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.0
DANN	Benign	0.55
PhyloP100		-0.17
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: rs12740374; hg19: chr1-109817590; COSMIC: COSV54781525; COSMIC: COSV54781525;