rs3774207

Variant names:

• chr3-9943972-C-T
• rs3774207
• ENST00000326434.9:c.1119C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-9943972-C-T
• chr3-9943972-C-A
• chr3-9943972-C-G

Variant summary

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

The NM_001374317.1(CRELD1):​c.1131C>T​(p.His377His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 1,106,654 control chromosomes in the GnomAD database, including 48,973 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (13892 hom., cov: 32)
  • Exomes 𝑓: 0.25 (35081 hom.)
• Consequence: CRELD1 NM_001374317.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.270
• Publications: 31 publications found

Genes affected

CRELD1 (HGNC:14630): (cysteine rich with EGF like domains 1) This gene encodes a member of a subfamily of epidermal growth factor-related proteins. The encoded protein is characterized by a cysteine-rich with epidermal growth factor-like domain. This protein may function as a cell adhesion molecule. Mutations in this gene are the cause of atrioventricular septal defect. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Apr 2010]

ENSG00000288550 (HGNC:):

PRRT3 (HGNC:26591): (proline rich transmembrane protein 3) Predicted to be integral component of membrane. [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=-0.9).
• BP6: Variant 3-9943972-C-T is Benign according to our data. Variant chr3-9943972-C-T is described in ClinVar as Benign. ClinVar VariationId is 137030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.27 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001374317.1. 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
	CRELD1	NM_001077415.3	MANE Select	c.1049-393C>T		intron	N/A	NP_001070883.2	Q96HD1-1
	CRELD1	NM_001374317.1		c.1131C>T	p.His377His	synonymous	Exon 11 of 12	NP_001361246.1	A0A804HJJ0
	CRELD1	NM_001374318.1		c.1131C>T	p.His377His	synonymous	Exon 10 of 11	NP_001361247.1	A0A804HJJ0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRELD1	ENST00000326434.9	TSL:1	c.1119C>T	p.His373His	synonymous	Exon 11 of 12	ENSP00000321856.5	Q96HD1-2
	CRELD1	ENST00000452070.6	TSL:2 MANE Select	c.1049-393C>T		intron	N/A	ENSP00000393643.2	Q96HD1-1
	CRELD1	ENST00000383811.8	TSL:1	c.1049-393C>T		intron	N/A	ENSP00000373322.3	Q96HD1-1

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55816 AN: 151994 Hom.: 13874 Cov.: 32

Gnomad AFR AF: 0.715

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.323

GnomAD2 exomes AF: 0.272 AC: 67640 AN: 249032 AF XY: 0.262

Gnomad AFR exome AF: 0.730

Gnomad AMR exome AF: 0.308

Gnomad ASJ exome AF: 0.294

Gnomad EAS exome AF: 0.183

Gnomad FIN exome AF: 0.159

Gnomad NFE exome AF: 0.234

Gnomad OTH exome AF: 0.252

GnomAD4 exome AF: 0.254 AC: 242391 AN: 954542 Hom.: 35081 Cov.: 14 AF XY: 0.252 AC XY: 125093 AN XY: 496204

African (AFR) AF: 0.727 AC: 17368 AN: 23898

American (AMR) AF: 0.308 AC: 13611 AN: 44122

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 6698 AN: 22978

East Asian (EAS) AF: 0.225 AC: 8400 AN: 37398

South Asian (SAS) AF: 0.260 AC: 19761 AN: 76122

European-Finnish (FIN) AF: 0.164 AC: 8708 AN: 53238

Middle Eastern (MID) AF: 0.252 AC: 1200 AN: 4766

European-Non Finnish (NFE) AF: 0.239 AC: 154771 AN: 648184

Other (OTH) AF: 0.271 AC: 11874 AN: 43836

GnomAD4 genome AF: 0.367 AC: 55884 AN: 152112 Hom.: 13892 Cov.: 32 AF XY: 0.357 AC XY: 26525 AN XY: 74368

African (AFR) AF: 0.714 AC: 29632 AN: 41478

American (AMR) AF: 0.276 AC: 4222 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1011 AN: 3472

East Asian (EAS) AF: 0.186 AC: 960 AN: 5172

South Asian (SAS) AF: 0.266 AC: 1281 AN: 4824

European-Finnish (FIN) AF: 0.151 AC: 1600 AN: 10590

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.237 AC: 16136 AN: 67982

Other (OTH) AF: 0.321 AC: 676 AN: 2108

Alfa AF: 0.302 Hom.: 22193

Bravo AF: 0.395

Asia WGS AF: 0.232 AC: 809 AN: 3478

EpiCase AF: 0.245

EpiControl AF: 0.238

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Atrioventricular septal defect, susceptibility to, 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.46
PhyloP100		-0.27
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: rs3774207; hg19: chr3-9985656; COSMIC: COSV55976326; COSMIC: COSV55976326;