rs6728

Variant names:

• chr17-78674151-C-G
• rs6728
• NM_004762.6:c.*1940G>C

Variant summary

Our verdict is Benign. The variant received -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
• 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]

ENSG00000294389 (HGNC:):

ACMG classification

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.

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.*1940G>C		3_prime_UTR	Exon 14 of 14	NP_004753.1	Q15438-1
	CYTH1	NM_001365040.2		c.*1940G>C		3_prime_UTR	Exon 13 of 13	NP_001351969.1	K7ENQ8
	CYTH1	NM_017456.4		c.*1940G>C		3_prime_UTR	Exon 13 of 13	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.*1940G>C		3_prime_UTR	Exon 14 of 14	ENSP00000389095.3	Q15438-1
	CYTH1	ENST00000589768.6	TSL:3	c.*1940G>C		3_prime_UTR	Exon 13 of 13	ENSP00000467052.2	K7ENQ8
	CYTH1	ENST00000591455.5	TSL:2	c.*1940G>C		3_prime_UTR	Exon 13 of 13	ENSP00000465665.1	Q15438-2

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.222 AC: 94 AN: 424

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.500 AC: 2 AN: 4

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

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: 62 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14250 AN: 68000

Other (OTH) AF: 0.198 AC: 419 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	17
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)

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: rs6728; hg19: chr17-76670233;