chr3-46979900-C-T

Variant names:

• chr3-46979900-C-T
• rs1575573407
• NM_015175.3:c.39C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_015175.3(NBEAL2):​c.39C>T​(p.Leu13Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NBEAL2 NM_015175.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.661
• Publications: 0 publications found

Genes affected

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]

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]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 3-46979900-C-T is Benign according to our data. Variant chr3-46979900-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 753173.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.661 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015175.3. 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
	NBEAL2	NM_015175.3	MANE Select	c.39C>T	p.Leu13Leu	synonymous	Exon 1 of 54	NP_055990.1	Q6ZNJ1-1
	CCDC12	NM_144716.6		c.-73+2032G>A		intron	N/A	NP_653317.2	J3KR35

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NBEAL2	ENST00000450053.8	TSL:2 MANE Select	c.39C>T	p.Leu13Leu	synonymous	Exon 1 of 54	ENSP00000415034.2	Q6ZNJ1-1
	NBEAL2	ENST00000933460.1		c.39C>T	p.Leu13Leu	synonymous	Exon 1 of 52	ENSP00000603519.1
	NBEAL2	ENST00000952756.1		c.39C>T	p.Leu13Leu	synonymous	Exon 1 of 52	ENSP00000622815.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 299752 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 164410

African (AFR) AF: 0.00 AC: 0 AN: 7524

American (AMR) AF: 0.00 AC: 0 AN: 14532

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11848

East Asian (EAS) AF: 0.00 AC: 0 AN: 20808

South Asian (SAS) AF: 0.00 AC: 0 AN: 19218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25536

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1492

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 181464

Other (OTH) AF: 0.00 AC: 0 AN: 17330

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	8.7
DANN	Benign	0.96
PhyloP100		-0.66
PromoterAI		-0.068	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1575573407; hg19: chr3-47021390;