3-9934475-A-G

Position:

• chr3-9934475-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001077415.3(CRELD1):​c.37A>G​(p.Met13Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.99 in 1,613,982 control chromosomes in the GnomAD database, including 790,642 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.99 (74939 hom., cov: 30)
  • Exomes 𝑓: 0.99 (715703 hom.)
• Consequence: CRELD1 NM_001077415.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.403

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.5156565E-7).
• BP6: Variant 3-9934475-A-G is Benign according to our data. Variant chr3-9934475-A-G is described in ClinVar as [Benign]. Clinvar id is 1164100.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-9934475-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRELD1	NM_001077415.3	c.37A>G	p.Met13Val	missense_variant	2/11	ENST00000452070.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRELD1	ENST00000452070.6	c.37A>G	p.Met13Val	missense_variant	2/11	2	NM_001077415.3	P1

Frequencies

GnomAD3 genomes AF: 0.992 AC: 150936 AN: 152132 Hom.: 74878 Cov.: 30

Gnomad AFR AF: 0.998

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.991

Gnomad ASJ AF: 0.988

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.990

Gnomad FIN AF: 0.998

Gnomad MID AF: 0.997

Gnomad NFE AF: 0.988

Gnomad OTH AF: 0.990

GnomAD3 exomes AF: 0.991 AC: 249146 AN: 251350 Hom.: 123485 AF XY: 0.991 AC XY: 134618 AN XY: 135884

Gnomad AFR exome AF: 0.998

Gnomad AMR exome AF: 0.993

Gnomad ASJ exome AF: 0.990

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 0.989

Gnomad FIN exome AF: 0.998

Gnomad NFE exome AF: 0.988

Gnomad OTH exome AF: 0.992

GnomAD4 exome AF: 0.990 AC: 1446473 AN: 1461732 Hom.: 715703 Cov.: 55 AF XY: 0.990 AC XY: 719552 AN XY: 727168

Gnomad4 AFR exome AF: 0.998

Gnomad4 AMR exome AF: 0.993

Gnomad4 ASJ exome AF: 0.989

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.989

Gnomad4 FIN exome AF: 0.997

Gnomad4 NFE exome AF: 0.988

Gnomad4 OTH exome AF: 0.991

GnomAD4 genome AF: 0.992 AC: 151056 AN: 152250 Hom.: 74939 Cov.: 30 AF XY: 0.992 AC XY: 73843 AN XY: 74428

Gnomad4 AFR AF: 0.998

Gnomad4 AMR AF: 0.991

Gnomad4 ASJ AF: 0.988

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.990

Gnomad4 FIN AF: 0.998

Gnomad4 NFE AF: 0.988

Gnomad4 OTH AF: 0.991

Alfa AF: 0.989 Hom.: 160961

Bravo AF: 0.992

TwinsUK AF: 0.989 AC: 3669

ALSPAC AF: 0.991 AC: 3818

ESP6500AA AF: 0.998 AC: 4399

ESP6500EA AF: 0.988 AC: 8496

ExAC AF: 0.992 AC: 120388

Asia WGS AF: 0.997 AC: 3466 AN: 3478

EpiCase AF: 0.987

EpiControl AF: 0.988

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Atrioventricular septal defect, susceptibility to, 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	1.6
DANN	Benign	0.68
DEOGEN2	Benign	0.00068	T;T;T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.12	.;.;T;T
MetaRNN	Benign	9.5e-7	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N;N;N;N
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.11	N;N;N;N
REVEL	Benign	0.064
Sift	Benign	0.55	T;T;T;T
Sift4G	Benign	0.86	T;T;T;T
Polyphen		0.0	B;B;B;B
Vest4		0.061
MPC		0.16
ClinPred		0.0013	T
GERP RS		0.33
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.032
gMVP		0.21

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

Publications

LitVar

Other links and lift over

dbSNP: rs279552; hg19: chr3-9976159;