dbSNP rs6728: CYTH1:c.*1940G>C (chr17-78674151-C-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_004762.6(CYTH1):c.*1940G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,662 control chromosomes in the GnomAD database, including 2,561 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 0.18 ( 2551 hom., cov: 33)

Exomes 𝑓: 0.22 ( 10 hom. )

Consequence

CYTH1
NM_004762.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.60

Publications

13 publications found

Variant links:

Genes affected

CYTH1 (HGNC:9501): (cytohesin 1) The protein encoded by this gene is a member of the PSCD family. Members of this family have identical structural organization that consists of an N-terminal coiled-coil motif, a central Sec7 domain, and a C-terminal pleckstrin homology (PH) domain. The coiled-coil motif is involved in homodimerization, the Sec7 domain contains guanine-nucleotide exchange protein activity, and the PH domain interacts with phospholipids and is responsible for association of PSCDs with membranes. Members of this family appear to mediate the regulation of protein sorting and membrane trafficking. This gene is highly expressed in natural killer and peripheral T cells, and regulates the adhesiveness of integrins at the plasma membrane of lymphocytes. A pseudogene of this gene has been defined on the X chromosome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

CYTH1 links:

ENSG00000294389 (HGNC:):

ENSG00000294389 links:

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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=-0.41).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYTH1	NM_004762.6 link	c.*1940G>C		3_prime_UTR_variant	Exon 14 of 14	ENST00000446868.8	NP_004753.1	Q15438-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYTH1	ENST00000446868.8 link	c.*1940G>C		3_prime_UTR_variant	Exon 14 of 14	5	NM_004762.6	ENSP00000389095.3		Q15438-1

Frequencies

GnomAD3 genomes

AF:

0.179

AC:

27159

AN:

152114

Hom.:

2553

Cov.:

show subpopulations

Gnomad AFR

AF:

0.159

Gnomad AMI

AF:

0.0943

Gnomad AMR

AF:

0.126

Gnomad ASJ

AF:

0.214

Gnomad EAS

AF:

0.0663

Gnomad SAS

AF:

0.107

Gnomad FIN

AF:

0.209

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.209

Gnomad OTH

AF:

0.197

GnomAD4 exome

AF:

0.223

AC:

AN:

430

Hom.:

Cov.:

AF XY:

0.221

AC XY:

AN XY:

258

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.222

AC:

AN:

424

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.414

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.179

AC:

27174

AN:

152232

Hom.:

2551

Cov.:

AF XY:

0.176

AC XY:

13108

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.159

AC:

6613

AN:

41530

American (AMR)

AF:

0.126

AC:

1928

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.214

AC:

743

AN:

3472

East Asian (EAS)

AF:

0.0665

AC:

345

AN:

5188

South Asian (SAS)

AF:

0.106

AC:

514

AN:

4830

European-Finnish (FIN)

AF:

0.209

AC:

2214

AN:

10588

Middle Eastern (MID)

AF:

0.211

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.210

AC:

14250

AN:

68000

Other (OTH)

AF:

0.198

AC:

419

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1173

2346

3520

4693

5866

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

288

576

864

1152

1440

<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:

0.199

Hom.:

400

Bravo

AF:

0.170

Asia WGS

AF:

0.105

AC:

363

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.84

PhyloP100

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over