chr3-9943171-C-T

Variant names:

• chr3-9943171-C-T
• rs79223485
• NM_001077415.3:c.912C>T

Variant summary

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

The NM_001077415.3(CRELD1):​c.912C>T​(p.Leu304Leu) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00366 in 1,612,092 control chromosomes in the GnomAD database, including 183 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (89 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (94 hom.)
• Consequence: CRELD1 NM_001077415.3 splice_region, synonymous
• Scores: Splicing: ADA: 0.0009384
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.883
• Publications: 4 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=-0.51).
• BP6: Variant 3-9943171-C-T is Benign according to our data. Variant chr3-9943171-C-T is described in ClinVar as Benign. ClinVar VariationId is 137034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.883 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0637 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077415.3. 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
	CRELD1	NM_001077415.3	MANE Select	c.912C>T	p.Leu304Leu	splice_region synonymous	Exon 9 of 11	NP_001070883.2	Q96HD1-1
	CRELD1	NM_001374317.1		c.912C>T	p.Leu304Leu	splice_region synonymous	Exon 9 of 12	NP_001361246.1	A0A804HJJ0
	CRELD1	NM_001374318.1		c.912C>T	p.Leu304Leu	splice_region synonymous	Exon 8 of 11	NP_001361247.1	A0A804HJJ0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRELD1	ENST00000452070.6	TSL:2 MANE Select	c.912C>T	p.Leu304Leu	splice_region synonymous	Exon 9 of 11	ENSP00000393643.2	Q96HD1-1
	CRELD1	ENST00000326434.9	TSL:1	c.912C>T	p.Leu304Leu	splice_region synonymous	Exon 9 of 12	ENSP00000321856.5	Q96HD1-2
	CRELD1	ENST00000383811.8	TSL:1	c.912C>T	p.Leu304Leu	splice_region synonymous	Exon 8 of 10	ENSP00000373322.3	Q96HD1-1

Frequencies

GnomAD3 genomes AF: 0.0187 AC: 2851 AN: 152104 Hom.: 88 Cov.: 32

Gnomad AFR AF: 0.0658

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00569

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00813

GnomAD2 exomes AF: 0.00481 AC: 1204 AN: 250550 AF XY: 0.00346

Gnomad AFR exome AF: 0.0656

Gnomad AMR exome AF: 0.00281

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000158

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00208 AC: 3043 AN: 1459870 Hom.: 94 Cov.: 31 AF XY: 0.00181 AC XY: 1312 AN XY: 726272

African (AFR) AF: 0.0688 AC: 2301 AN: 33460

American (AMR) AF: 0.00362 AC: 162 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.000383 AC: 33 AN: 86226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52108

Middle Eastern (MID) AF: 0.00295 AC: 17 AN: 5768

European-Non Finnish (NFE) AF: 0.000250 AC: 278 AN: 1111402

Other (OTH) AF: 0.00417 AC: 252 AN: 60362

GnomAD4 genome AF: 0.0188 AC: 2857 AN: 152222 Hom.: 89 Cov.: 32 AF XY: 0.0183 AC XY: 1364 AN XY: 74420

African (AFR) AF: 0.0658 AC: 2731 AN: 41516

American (AMR) AF: 0.00562 AC: 86 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68008

Other (OTH) AF: 0.00805 AC: 17 AN: 2112

Alfa AF: 0.00663 Hom.: 64

Bravo AF: 0.0205

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	11
DANN	Benign	0.78
PhyloP100		-0.88
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Mutation Taster		=72/28	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00094
dbscSNV1_RF	Benign	0.21
SpliceAI score (max)		0.090		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: rs79223485; hg19: chr3-9984855;