17-78697469-C-G

Variant names:

• chr17-78697469-C-G
• rs10512617
• NM_004762.6:c.811+800G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004762.6. 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
	CYTH1	NM_004762.6	MANE Select	c.811+800G>C		intron	N/A	NP_004753.1	Q15438-1
	CYTH1	NM_001365040.2		c.817+800G>C		intron	N/A	NP_001351969.1	K7ENQ8
	CYTH1	NM_017456.4		c.811+800G>C		intron	N/A	NP_059430.2	Q15438-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYTH1	ENST00000446868.8	TSL:5 MANE Select	c.811+800G>C		intron	N/A	ENSP00000389095.3	Q15438-1
	CYTH1	ENST00000589768.6	TSL:3	c.817+800G>C		intron	N/A	ENSP00000467052.2	K7ENQ8
	CYTH1	ENST00000591455.5	TSL:2	c.811+800G>C		intron	N/A	ENSP00000465665.1	Q15438-2

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

African (AFR) AF: 0.120 AC: 4991 AN: 41462

American (AMR) AF: 0.419 AC: 6390 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1754 AN: 3470

East Asian (EAS) AF: 0.423 AC: 2186 AN: 5168

South Asian (SAS) AF: 0.379 AC: 1823 AN: 4812

European-Finnish (FIN) AF: 0.612 AC: 6443 AN: 10520

Middle Eastern (MID) AF: 0.408 AC: 119 AN: 292

European-Non Finnish (NFE) AF: 0.537 AC: 36460 AN: 67940

Other (OTH) AF: 0.424 AC: 893 AN: 2104

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.6
DANN	Benign	0.52
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

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: rs10512617; hg19: chr17-76693551;