19-45053404-A-G

Variant names:

• chr19-45053404-A-G
• rs10416445
• NM_007056.3:c.379+227A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007056.3(CLASRP):​c.379+227A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 151,998 control chromosomes in the GnomAD database, including 16,121 homozygotes. 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: 𝑓 0.46 (16121 hom., cov: 32)
• Consequence: CLASRP NM_007056.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.276
• Publications: 14 publications found

Genes affected

CLASRP (HGNC:17731): (CLK4 associating serine/arginine rich protein) Predicted to be involved in RNA splicing and mRNA processing. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007056.3. 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
	CLASRP	NM_007056.3	MANE Select	c.379+227A>G		intron	N/A	NP_008987.2
	CLASRP	NM_001278439.2		c.193+227A>G		intron	N/A	NP_001265368.1
	CLASRP	NR_103529.2		n.472+227A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLASRP	ENST00000221455.8	TSL:1 MANE Select	c.379+227A>G		intron	N/A	ENSP00000221455.3
	CLASRP	ENST00000391952.7	TSL:1	n.379+227A>G		intron	N/A	ENSP00000375814.2
	CLASRP	ENST00000587112.1	TSL:1	n.322+227A>G		intron	N/A	ENSP00000466371.1

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69246 AN: 151880 Hom.: 16121 Cov.: 32

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.497

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.473

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.456 AC: 69270 AN: 151998 Hom.: 16121 Cov.: 32 AF XY: 0.454 AC XY: 33727 AN XY: 74296

African (AFR) AF: 0.372 AC: 15407 AN: 41414

American (AMR) AF: 0.445 AC: 6799 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 1612 AN: 3472

East Asian (EAS) AF: 0.411 AC: 2126 AN: 5172

South Asian (SAS) AF: 0.386 AC: 1856 AN: 4806

European-Finnish (FIN) AF: 0.497 AC: 5251 AN: 10576

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.509 AC: 34614 AN: 67976

Other (OTH) AF: 0.475 AC: 1002 AN: 2110

Alfa AF: 0.489 Hom.: 78128

Bravo AF: 0.449

Asia WGS AF: 0.421 AC: 1464 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.44
PhyloP100		0.28
Mutation Taster		=100/0	polymorphism (auto)

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: rs10416445; hg19: chr19-45556662;