12-30713849-T-A

Variant names:

• chr12-30713849-T-A
• rs769030647
• NM_001385503.1:c.2441A>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001385503.1(CAPRIN2):​c.2441A>T​(p.Asn814Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N814S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CAPRIN2 NM_001385503.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.78
• Publications: 0 publications found

Genes affected

CAPRIN2 (HGNC:21259): (caprin family member 2) The protein encoded by this gene may regulate the transport of mRNA. It may play a role in the differentiation of erythroblasts. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32106453).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385503.1. 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
	CAPRIN2	NM_001385503.1	MANE Select	c.2441A>T	p.Asn814Ile	missense	Exon 17 of 19	NP_001372432.1	F5H5J8
	CAPRIN2	NM_001002259.3		c.2687A>T	p.Asn896Ile	missense	Exon 16 of 18	NP_001002259.1	Q6IMN6-1
	CAPRIN2	NM_001319843.2		c.2684A>T	p.Asn895Ile	missense	Exon 16 of 18	NP_001306772.1	Q6IMN6-9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAPRIN2	ENST00000695402.1	MANE Select	c.2441A>T	p.Asn814Ile	missense	Exon 17 of 19	ENSP00000511883.1	F5H5J8
	CAPRIN2	ENST00000298892.9	TSL:1	c.2537A>T	p.Asn846Ile	missense	Exon 15 of 17	ENSP00000298892.5	Q6IMN6-2
	CAPRIN2	ENST00000417045.5	TSL:1	c.2684A>T	p.Asn895Ile	missense	Exon 16 of 18	ENSP00000391479.1	Q6IMN6-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250682 AF XY: 0.00000738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457020 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 725136

African (AFR) AF: 0.00 AC: 0 AN: 33388

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26052

East Asian (EAS) AF: 0.00 AC: 0 AN: 39618

South Asian (SAS) AF: 0.00 AC: 0 AN: 86104

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53264

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107922

Other (OTH) AF: 0.0000166 AC: 1 AN: 60208

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	23
DANN	Uncertain	0.99
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.76	T
PhyloP100		2.8
PrimateAI	Benign	0.41	T
PROVEAN	Pathogenic	-6.1	D
REVEL	Benign	0.20
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.96	D
Vest4		0.77
MVP		0.31
MPC		0.37
ClinPred		0.99	D
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.49
Mutation Taster		=78/22	polymorphism

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: rs769030647; hg19: chr12-30866783;