NM_001385503.1:c.2418T>C

Variant names:

• chr12-30713872-A-G
• rs3213895
• NM_001385503.1:c.2418T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001385503.1(CAPRIN2):​c.2418T>C​(p.Tyr806Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00192 in 1,593,526 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0081 (18 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (33 hom.)
• Consequence: CAPRIN2 NM_001385503.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0660
• Publications: 5 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 12-30713872-A-G is Benign according to our data. Variant chr12-30713872-A-G is described in ClinVar as Benign. ClinVar VariationId is 786224.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00808 (1231/152316) while in subpopulation AFR AF = 0.0275 (1143/41574). AF 95% confidence interval is 0.0262. There are 18 homozygotes in GnomAd4. There are 570 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 18 AR gene

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.2418T>C	p.Tyr806Tyr	synonymous	Exon 17 of 19	NP_001372432.1	F5H5J8
	CAPRIN2	NM_001002259.3		c.2664T>C	p.Tyr888Tyr	synonymous	Exon 16 of 18	NP_001002259.1	Q6IMN6-1
	CAPRIN2	NM_001319843.2		c.2661T>C	p.Tyr887Tyr	synonymous	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.2418T>C	p.Tyr806Tyr	synonymous	Exon 17 of 19	ENSP00000511883.1	F5H5J8
	CAPRIN2	ENST00000298892.9	TSL:1	c.2514T>C	p.Tyr838Tyr	synonymous	Exon 15 of 17	ENSP00000298892.5	Q6IMN6-2
	CAPRIN2	ENST00000417045.5	TSL:1	c.2661T>C	p.Tyr887Tyr	synonymous	Exon 16 of 18	ENSP00000391479.1	Q6IMN6-3

Frequencies

GnomAD3 genomes AF: 0.00808 AC: 1230 AN: 152198 Hom.: 18 Cov.: 32

Gnomad AFR AF: 0.0276

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00520

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.00217 AC: 543 AN: 249774 AF XY: 0.00168

Gnomad AFR exome AF: 0.0285

Gnomad AMR exome AF: 0.000755

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00196

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000177

Gnomad OTH exome AF: 0.000494

GnomAD4 exome AF: 0.00127 AC: 1829 AN: 1441210 Hom.: 33 Cov.: 25 AF XY: 0.00115 AC XY: 829 AN XY: 718142

African (AFR) AF: 0.0288 AC: 950 AN: 33022

American (AMR) AF: 0.000941 AC: 42 AN: 44610

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25960

East Asian (EAS) AF: 0.0164 AC: 646 AN: 39502

South Asian (SAS) AF: 0.0000467 AC: 4 AN: 85624

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53048

Middle Eastern (MID) AF: 0.00157 AC: 9 AN: 5726

European-Non Finnish (NFE) AF: 0.0000850 AC: 93 AN: 1094046

Other (OTH) AF: 0.00142 AC: 85 AN: 59672

GnomAD4 genome AF: 0.00808 AC: 1231 AN: 152316 Hom.: 18 Cov.: 32 AF XY: 0.00765 AC XY: 570 AN XY: 74490

African (AFR) AF: 0.0275 AC: 1143 AN: 41574

American (AMR) AF: 0.00229 AC: 35 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00522 AC: 27 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 68026

Other (OTH) AF: 0.00473 AC: 10 AN: 2116

Alfa AF: 0.00280 Hom.: 9

Bravo AF: 0.00859

Asia WGS AF: 0.00202 AC: 8 AN: 3478

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	-0.61
CADD	Benign	7.0
DANN	Benign	0.40
PhyloP100		-0.066
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.20		Position offset: -3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3213895; hg19: chr12-30866806; COSMIC: COSV99195401; COSMIC: COSV99195401;