rs608418

Variant names:

• chr12-9979266-T-A
• rs608418
• NM_138337.6:c.191-70T>A

Your query was ambiguous. Multiple possible variants found:

• chr12-9979266-T-A
• chr12-9979266-T-C
• chr12-9979266-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_138337.6(CLEC12A):​c.191-70T>A variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 9.3e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CLEC12A NM_138337.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.45
• Publications: 14 publications found

Genes affected

CLEC12A (HGNC:31713): (C-type lectin domain family 12 member A) This gene encodes a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. Members of this family share a common protein fold and have diverse functions, such as cell adhesion, cell-cell signaling, glycoprotein turnover, and roles in inflammation and immune response. The protein encoded by this gene is a negative regulator of granulocyte and monocyte function. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. This gene is closely linked to other CTL/CTLD superfamily members in the natural killer gene complex region on chromosome 12p13. [provided by RefSeq, May 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138337.6. 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
	CLEC12A	NM_138337.6	MANE Select	c.191-70T>A		intron	N/A	NP_612210.4
	CLEC12A	NM_001207010.2		c.221-70T>A		intron	N/A	NP_001193939.1	Q5QGZ9-1
	CLEC12A	NM_201623.4		c.92-70T>A		intron	N/A	NP_963917.2	Q5QGZ9-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC12A	ENST00000304361.9	TSL:1 MANE Select	c.191-70T>A		intron	N/A	ENSP00000302804.4	Q5QGZ9-2
	CLEC12A	ENST00000355690.8	TSL:1	c.221-70T>A		intron	N/A	ENSP00000347916.4	Q5QGZ9-1
	CLEC12A	ENST00000350667.4	TSL:1	c.92-70T>A		intron	N/A	ENSP00000345448.4	Q5QGZ9-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.28e-7 AC: 1 AN: 1077878 Hom.: 0 Cov.: 14 AF XY: 0.00 AC XY: 0 AN XY: 545224

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 24114

American (AMR) AF: 0.00 AC: 0 AN: 28754

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22522

East Asian (EAS) AF: 0.00 AC: 0 AN: 34444

South Asian (SAS) AF: 0.00 AC: 0 AN: 68906

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4332

European-Non Finnish (NFE) AF: 0.00000125 AC: 1 AN: 801530

Other (OTH) AF: 0.00 AC: 0 AN: 46878

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	13
DANN	Benign	0.75
PhyloP100		2.4

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: rs608418; hg19: chr12-10131865;