dbSNP rs200017484: CHLSN:c.405+3G>A (chr7-1000467-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001424329.1(CHLSN):c.17G>A(p.Cys6Tyr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000519 in 1,598,442 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 7/7 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0026 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00030 ( 8 hom. )

Consequence

CHLSN
NM_001424329.1 missense, splice_region

Scores

Splicing: ADA: 0.00007144

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.328

Publications

0 publications found

Variant links:

Genes affected

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

CHLSN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 7-1000467-C-T is Benign according to our data. Variant chr7-1000467-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2657175.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001424329.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHLSN	NM_001318252.2	MANE Select	c.405+3G>A		splice_region intron	N/A	NP_001305181.1	Q9BRJ6
CHLSN	NM_001424329.1		c.17G>A	p.Cys6Tyr	missense splice_region	Exon 3 of 4	NP_001411258.1
CHLSN	NM_001424325.1		c.405+3G>A		splice_region intron	N/A	NP_001411254.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHLSN	ENST00000397098.8	TSL:1 MANE Select	c.405+3G>A	splice_region intron	N/A	ENSP00000380286.3	Q9BRJ6
CHLSN	ENST00000357429.10	TSL:1	c.405+3G>A	splice_region intron	N/A	ENSP00000350011.5	Q9BRJ6
CHLSN	ENST00000397100.6	TSL:3	c.405+3G>A	splice_region intron	N/A	ENSP00000380288.2	Q9BRJ6

Frequencies

GnomAD3 genomes

AF:

0.00257

AC:

390

AN:

151884

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00881

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00192

GnomAD2 exomes

AF:

0.000694

AC:

158

AN:

227528

AF XY:

0.000527

show subpopulations

Gnomad AFR exome

AF:

0.00943

Gnomad AMR exome

AF:

0.000649

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000295

Gnomad OTH exome

AF:

0.000531

GnomAD4 exome

AF:

0.000304

AC:

440

AN:

1446442

Hom.:

Cov.:

AF XY:

0.000265

AC XY:

190

AN XY:

718294

show subpopulations

African (AFR)

AF:

0.0105

AC:

350

AN:

33280

American (AMR)

AF:

0.000765

AC:

AN:

43136

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25782

East Asian (EAS)

AF:

0.00

AC:

AN:

39400

South Asian (SAS)

AF:

0.0000595

AC:

AN:

84072

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50794

Middle Eastern (MID)

AF:

0.000870

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.00000815

AC:

AN:

1104372

Other (OTH)

AF:

0.000635

AC:

AN:

59858

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

103

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00256

AC:

389

AN:

152000

Hom.:

Cov.:

AF XY:

0.00262

AC XY:

195

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.00876

AC:

363

AN:

41458

American (AMR)

AF:

0.00131

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10576

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67940

Other (OTH)

AF:

0.00190

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

102

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00153

Hom.:

Bravo

AF:

0.00296

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

5.6

(source)

DANN

Benign

0.82

PhyloP100

-0.33

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000071

dbscSNV1_RF

Benign

0.084

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over