rs1405310498

Variant names:

• chr7-1010065-G-C
• rs1405310498
• NM_001318252.2:c.208C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001318252.2(CHLSN):​c.208C>G​(p.Leu70Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: CHLSN NM_001318252.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.61
• Publications: 0 publications found

Genes affected

CHLSN (HGNC:22421): (chromosome 7 open reading frame 50) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13979512).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318252.2. 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
	CHLSN	NM_001318252.2	MANE Select	c.208C>G	p.Leu70Val	missense	Exon 3 of 5	NP_001305181.1	Q9BRJ6
	CHLSN	NM_001424325.1		c.208C>G	p.Leu70Val	missense	Exon 3 of 6	NP_001411254.1
	CHLSN	NM_001424326.1		c.208C>G	p.Leu70Val	missense	Exon 3 of 6	NP_001411255.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHLSN	ENST00000397098.8	TSL:1 MANE Select	c.208C>G	p.Leu70Val	missense	Exon 3 of 5	ENSP00000380286.3	Q9BRJ6
	CHLSN	ENST00000357429.10	TSL:1	c.208C>G	p.Leu70Val	missense	Exon 3 of 5	ENSP00000350011.5	Q9BRJ6
	CHLSN	ENST00000397100.6	TSL:3	c.208C>G	p.Leu70Val	missense	Exon 3 of 5	ENSP00000380288.2	Q9BRJ6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1460134 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 726434

African (AFR) AF: 0.000119 AC: 4 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51828

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111928

Other (OTH) AF: 0.0000166 AC: 1 AN: 60374

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.6
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.15
Sift	Benign	0.043	D
Sift4G	Uncertain	0.013	D
Polyphen		0.20	B
Vest4		0.12
MutPred		0.16		Gain of methylation at K71 (P = 0.0331)
MVP		0.59
MPC		0.050
ClinPred		0.16	T
GERP RS		3.8
Varity_R		0.14
gMVP		0.19
Mutation Taster		=83/17	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: rs1405310498; hg19: chr7-1049701;