Genetic Variant NM_001077415.3:c.1048+258T>C (chr3-9943773-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.882

Publications

17 publications found

Variant links:

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]

CRELD1 links:

ENSG00000288550 (HGNC:):

ENSG00000288550 links:

PRRT3 (HGNC:26591): (proline rich transmembrane protein 3) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

PRRT3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CRELD1	NM_001077415.3	MANE Select	c.1048+258T>C	intron	N/A	NP_001070883.2	Q96HD1-1
CRELD1	NM_001410713.1		c.*22T>C	3_prime_UTR	Exon 11 of 11	NP_001397642.1	A0A804HKP7
CRELD1	NM_001374317.1		c.1049-117T>C	intron	N/A	NP_001361246.1	A0A804HJJ0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CRELD1	ENST00000452070.6	TSL:2 MANE Select	c.1048+258T>C	intron	N/A	ENSP00000393643.2	Q96HD1-1
CRELD1	ENST00000326434.9	TSL:1	c.1049-129T>C	intron	N/A	ENSP00000321856.5	Q96HD1-2
CRELD1	ENST00000383811.8	TSL:1	c.1048+258T>C	intron	N/A	ENSP00000373322.3	Q96HD1-1

Frequencies

GnomAD3 genomes

AF:

0.368

AC:

55946

AN:

151960

Hom.:

13918

Cov.:

show subpopulations

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.:

AF XY:

0.255

AC XY:

183745

AN XY:

720684

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

16079

32158

48236

64315

80394

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9448

18896

28344

37792

47240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.368

AC:

56012

AN:

152078

Hom.:

13936

Cov.:

AF XY:

0.358

AC XY:

26601

AN XY:

74354

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.238

AC:

16207

AN:

67990

Other (OTH)

AF:

0.323

AC:

682

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1471

2941

4412

5882

7353

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

492

984

1476

1968

2460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.285

Hom.:

9633

Bravo

AF:

0.396

Asia WGS

AF:

0.233

AC:

812

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.10

(source)

DANN

Benign

0.28

PhyloP100

-0.88

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over