10-12760948-G-C

Variant names:

• chr10-12760948-G-C
• rs149215581
• NM_153498.4:c.300G>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_153498.4(CAMK1D):​c.300G>C​(p.Leu100Leu) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000744 in 1,610,672 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00043 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00078 (0 hom.)
• Consequence: CAMK1D NM_153498.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.0008508
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.62
• Publications: 2 publications found

Genes affected

CAMK1D (HGNC:19341): (calcium/calmodulin dependent protein kinase ID) This gene is a member of the calcium/calmodulin-dependent protein kinase 1 family, a subfamily of the serine/threonine kinases. The encoded protein is a component of the calcium-regulated calmodulin-dependent protein kinase cascade. It has been associated with multiple processes including regulation of granulocyte function, activation of CREB-dependent gene transcription, aldosterone synthesis, differentiation and activation of neutrophil cells, and apoptosis of erythroleukemia cells. Alternatively spliced transcript variants encoding different isoforms of this gene have been described. [provided by RefSeq, Jan 2015]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0374552).
• BP6: Variant 10-12760948-G-C is Benign according to our data. Variant chr10-12760948-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3136773.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.62 with no splicing effect.
• BS2: High AC in GnomAd4 at 65 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMK1D	NM_153498.4	c.300G>C	p.Leu100Leu	splice_region_variant, synonymous_variant	Exon 4 of 11	ENST00000619168.5	NP_705718.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAMK1D	ENST00000619168.5	c.300G>C	p.Leu100Leu	splice_region_variant, synonymous_variant	Exon 4 of 11	1	NM_153498.4	ENSP00000478874.1
CAMK1D	ENST00000378845.5	c.300G>C	p.Leu100Leu	splice_region_variant, synonymous_variant	Exon 4 of 10	1		ENSP00000368122.1

Frequencies

GnomAD3 genomes AF: 0.000428 AC: 65 AN: 152014 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000568

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000765

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000284 AC: 71 AN: 250302 AF XY: 0.000251

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.0000997

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000508

Gnomad NFE exome AF: 0.000477

Gnomad OTH exome AF: 0.000328

GnomAD4 exome AF: 0.000777 AC: 1133 AN: 1458540 Hom.: 0 Cov.: 31 AF XY: 0.000747 AC XY: 542 AN XY: 725420

African (AFR) AF: 0.000150 AC: 5 AN: 33298

American (AMR) AF: 0.00 AC: 0 AN: 44172

Ashkenazi Jewish (ASJ) AF: 0.0000384 AC: 1 AN: 26048

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39668

South Asian (SAS) AF: 0.000186 AC: 16 AN: 85864

European-Finnish (FIN) AF: 0.000431 AC: 23 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.000935 AC: 1038 AN: 1110126

Other (OTH) AF: 0.000814 AC: 49 AN: 60224

GnomAD4 genome AF: 0.000427 AC: 65 AN: 152132 Hom.: 0 Cov.: 32 AF XY: 0.000336 AC XY: 25 AN XY: 74344

African (AFR) AF: 0.000120 AC: 5 AN: 41518

American (AMR) AF: 0.000131 AC: 2 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.000568 AC: 6 AN: 10556

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

European-Non Finnish (NFE) AF: 0.000765 AC: 52 AN: 67996

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000776 Hom.: 0

Bravo AF: 0.000378

TwinsUK AF: 0.00162 AC: 6

ALSPAC AF: 0.00130 AC: 5

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.000239 AC: 29

EpiCase AF: 0.000657

EpiControl AF: 0.000475

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Oct 20, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.20
DANN	Benign	0.53
DEOGEN2	Benign	0.011	T
FATHMM_MKL	Benign	0.064	N
LIST_S2	Uncertain	0.90	D
MetaRNN	Benign	0.037	T
PhyloP100		-2.6
Sift4G	Uncertain	0.0050	D
MVP		0.73
GERP RS		-7.0
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00085
dbscSNV1_RF	Benign	0.068
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: rs149215581; hg19: chr10-12802947;