rs13062516

Variant names:

• chr3-46979533-A-G
• rs13062516
• ENST00000605875.1:c.-108T>C

Your query was ambiguous. Multiple possible variants found:

• chr3-46979533-A-G
• chr3-46979533-A-T

Variant summary

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

The NM_144716.6(CCDC12):​c.-73+2399T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.952 in 194,522 control chromosomes in the GnomAD database, including 88,897 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.94 (68146 hom., cov: 34)
  • Exomes 𝑓: 0.99 (20751 hom.)
• Consequence: CCDC12 NM_144716.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.397
• Publications: 3 publications found

Genes affected

CCDC12 (HGNC:28332): (coiled-coil domain containing 12) Predicted to be part of U2-type spliceosomal complex and post-mRNA release spliceosomal complex. [provided by Alliance of Genome Resources, Apr 2022]

NBEAL2 (HGNC:31928): (neurobeachin like 2) The protein encoded by this gene contains a beige and Chediak-Higashi (BEACH) domain and multiple WD40 domains, and may play a role in megakaryocyte alpha-granule biogenesis. Mutations in this gene are a cause of gray platelet syndrome. [provided by RefSeq, Dec 2011]

NBEAL2 Gene-Disease associations (from GenCC):

• gray platelet syndrome

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 3-46979533-A-G is Benign according to our data. Variant chr3-46979533-A-G is described in ClinVar as Benign. ClinVar VariationId is 1251507.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144716.6. 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
	CCDC12	NM_144716.6		c.-73+2399T>C		intron	N/A	NP_653317.2	J3KR35
	NBEAL2	NM_015175.3	MANE Select	c.-329A>G		upstream_gene	N/A	NP_055990.1	Q6ZNJ1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC12	ENST00000605875.1	TSL:5	c.-108T>C		5_prime_UTR	Exon 1 of 4	ENSP00000473887.2	S4R331
	CCDC12	ENST00000292314.6	TSL:5	c.-73+2399T>C		intron	N/A	ENSP00000292314.2	J3KR35
	CCDC12	ENST00000425441.5	TSL:5	c.-215+2399T>C		intron	N/A	ENSP00000416263.2	Q8WUD4

Frequencies

GnomAD3 genomes AF: 0.942 AC: 143290 AN: 152134 Hom.: 68102 Cov.: 34

Gnomad AFR AF: 0.799

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.980

Gnomad ASJ AF: 0.995

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.952

GnomAD4 exome AF: 0.990 AC: 41858 AN: 42270 Hom.: 20751 Cov.: 0 AF XY: 0.991 AC XY: 21359 AN XY: 21548

African (AFR) AF: 0.808 AC: 1213 AN: 1502

American (AMR) AF: 0.980 AC: 1094 AN: 1116

Ashkenazi Jewish (ASJ) AF: 0.995 AC: 1755 AN: 1764

East Asian (EAS) AF: 1.00 AC: 3838 AN: 3838

South Asian (SAS) AF: 1.00 AC: 450 AN: 450

European-Finnish (FIN) AF: 1.00 AC: 3030 AN: 3030

Middle Eastern (MID) AF: 0.988 AC: 245 AN: 248

European-Non Finnish (NFE) AF: 0.999 AC: 27271 AN: 27298

Other (OTH) AF: 0.979 AC: 2962 AN: 3024

GnomAD4 genome AF: 0.942 AC: 143394 AN: 152252 Hom.: 68146 Cov.: 34 AF XY: 0.944 AC XY: 70286 AN XY: 74448

African (AFR) AF: 0.799 AC: 33169 AN: 41524

American (AMR) AF: 0.980 AC: 15003 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.995 AC: 3456 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5150 AN: 5150

South Asian (SAS) AF: 1.00 AC: 4830 AN: 4832

European-Finnish (FIN) AF: 1.00 AC: 10620 AN: 10620

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67948 AN: 68026

Other (OTH) AF: 0.953 AC: 2016 AN: 2116

Alfa AF: 0.961 Hom.: 4247

Bravo AF: 0.937

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.4
DANN	Benign	0.58
PhyloP100		-0.40
PromoterAI		-0.014	Neutral
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: rs13062516; hg19: chr3-47021023;