NM_001077415.3:c.1048+258T>C

Variant names:

• chr3-9943773-T-C
• rs9878047
• NM_001077415.3:c.1048+258T>C

Variant summary

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

The NM_001077415.3(CRELD1):​c.1048+258T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 1,601,580 control chromosomes in the GnomAD database, including 66,497 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (13936 hom., cov: 32)
  • Exomes 𝑓: 0.26 (52561 hom.)
• Consequence: CRELD1 NM_001077415.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.882
• Publications: 17 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 3-9943773-T-C is Benign according to our data. Variant chr3-9943773-T-C is described in ClinVar as Benign. ClinVar VariationId is 1276154.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRELD1	NM_001077415.3	c.1048+258T>C		intron_variant	Intron 10 of 10	ENST00000452070.6	NP_001070883.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRELD1	ENST00000452070.6	c.1048+258T>C		intron_variant	Intron 10 of 10	2	NM_001077415.3	ENSP00000393643.2
ENSG00000288550	ENST00000683484.1	n.*696+258T>C		intron_variant	Intron 23 of 23			ENSP00000507040.1

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55946 AN: 151960 Hom.: 13918 Cov.: 32

Gnomad AFR AF: 0.715

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.325

GnomAD4 exome AF: 0.257 AC: 371885 AN: 1449502 Hom.: 52561 Cov.: 34 AF XY: 0.255 AC XY: 183745 AN XY: 720684

African (AFR) AF: 0.735 AC: 24514 AN: 33356

American (AMR) AF: 0.310 AC: 13434 AN: 43286

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 7602 AN: 25808

East Asian (EAS) AF: 0.223 AC: 8834 AN: 39586

South Asian (SAS) AF: 0.261 AC: 22084 AN: 84726

European-Finnish (FIN) AF: 0.163 AC: 8047 AN: 49434

Middle Eastern (MID) AF: 0.276 AC: 1552 AN: 5618

European-Non Finnish (NFE) AF: 0.243 AC: 269507 AN: 1107588

Other (OTH) AF: 0.271 AC: 16311 AN: 60100

GnomAD4 genome AF: 0.368 AC: 56012 AN: 152078 Hom.: 13936 Cov.: 32 AF XY: 0.358 AC XY: 26601 AN XY: 74354

African (AFR) AF: 0.715 AC: 29634 AN: 41442

American (AMR) AF: 0.279 AC: 4265 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1010 AN: 3470

East Asian (EAS) AF: 0.187 AC: 962 AN: 5158

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

European-Finnish (FIN) AF: 0.151 AC: 1601 AN: 10596

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16207 AN: 67990

Other (OTH) AF: 0.323 AC: 682 AN: 2110

Alfa AF: 0.285 Hom.: 9633

Bravo AF: 0.396

Asia WGS AF: 0.233 AC: 812 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.10
DANN	Benign	0.28
PhyloP100		-0.88
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: rs9878047; hg19: chr3-9985457; COSMIC: COSV55977012; COSMIC: COSV55977012;