rs6728

Positions:

• chr17-78674151-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.60

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CYTH1	NM_004762.6	c.*1940G>C		3_prime_UTR_variant	14/14	ENST00000446868.8	NP_004753.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYTH1	ENST00000446868	c.*1940G>C		3_prime_UTR_variant	14/14	5	NM_004762.6	ENSP00000389095.3

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27159 AN: 152114 Hom.: 2553 Cov.: 33

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: 96 AN: 430 Hom.: 10 Cov.: 0 AF XY: 0.221 AC XY: 57 AN XY: 258

Gnomad4 FIN exome AF: 0.222

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.179 AC: 27174 AN: 152232 Hom.: 2551 Cov.: 33 AF XY: 0.176 AC XY: 13108 AN XY: 74434

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.0665

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.198

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	17
DANN	Benign	0.84
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

LitVar

Other links and lift over

dbSNP: rs6728; hg19: chr17-76670233;