17-78697469-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004762.6(CYTH1):c.811+800G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 151,940 control chromosomes in the GnomAD database, including 14,962 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 0.40 (14962 hom., cov: 31)
• Consequence: CYTH1 NM_004762.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.192

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYTH1	NM_004762.6	c.811+800G>C		intron_variant		ENST00000446868.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYTH1	ENST00000446868.8	c.811+800G>C		intron_variant		5	NM_004762.6	A1

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61379 AN: 151822 Hom.: 14961 Cov.: 31

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.395

Gnomad NFE AF: 0.537

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.404 AC: 61381 AN: 151940 Hom.: 14962 Cov.: 31 AF XY: 0.408 AC XY: 30325 AN XY: 74258

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.419

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.423

Gnomad4 SAS AF: 0.379

Gnomad4 FIN AF: 0.612

Gnomad4 NFE AF: 0.537

Gnomad4 OTH AF: 0.424

Alfa AF: 0.360 Hom.: 1260

Bravo AF: 0.373

Asia WGS AF: 0.401 AC: 1392 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	3.6
Dann	Benign	0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs10512617; hg19: chr17-76693551;