NM_004762.6:c.23-13028G>A

Variant names:

• chr17-78722760-C-T
• rs1552173
• NM_004762.6:c.23-13028G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004762.6(CYTH1):​c.23-13028G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 151,946 control chromosomes in the GnomAD database, including 20,199 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 0.51 (20199 hom., cov: 31)
• Consequence: CYTH1 NM_004762.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.03
• Publications: 15 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYTH1	NM_004762.6	c.23-13028G>A		intron_variant	Intron 1 of 13	ENST00000446868.8	NP_004753.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYTH1	ENST00000446868.8	c.23-13028G>A		intron_variant	Intron 1 of 13	5	NM_004762.6	ENSP00000389095.3

Frequencies

GnomAD3 genomes AF: 0.514 AC: 78061 AN: 151828 Hom.: 20191 Cov.: 31

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.502

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

GnomAD4 genome AF: 0.514 AC: 78114 AN: 151946 Hom.: 20199 Cov.: 31 AF XY: 0.519 AC XY: 38505 AN XY: 74258

African (AFR) AF: 0.468 AC: 19368 AN: 41390

American (AMR) AF: 0.479 AC: 7317 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.492 AC: 1704 AN: 3466

East Asian (EAS) AF: 0.516 AC: 2673 AN: 5182

South Asian (SAS) AF: 0.516 AC: 2487 AN: 4818

European-Finnish (FIN) AF: 0.607 AC: 6399 AN: 10538

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.538 AC: 36584 AN: 67964

Other (OTH) AF: 0.504 AC: 1063 AN: 2108

Alfa AF: 0.529 Hom.: 9510

Bravo AF: 0.495

Asia WGS AF: 0.533 AC: 1856 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.17
DANN	Benign	0.48
PhyloP100		-3.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1552173; hg19: chr17-76718842;