rs3735001

Variant names:

• chr7-135148462-C-A
• rs3735001
• NM_018295.5:c.-25+192C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-135148462-C-A
• chr7-135148462-C-G
• chr7-135148462-C-T

Variant summary

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

The NM_018295.5(TMEM140):​c.-25+192C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,190 control chromosomes in the GnomAD database, including 5,750 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 0.26 (5750 hom., cov: 33)
• Consequence: TMEM140 NM_018295.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.855
• Publications: 2 publications found

Genes affected

TMEM140 (HGNC:21870): (transmembrane protein 140) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

CYREN (HGNC:22432): (cell cycle regulator of NHEJ) Involved in double-strand break repair via nonhomologous end joining and negative regulation of double-strand break repair via nonhomologous end joining. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018295.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM140	NM_018295.5	MANE Select	c.-25+192C>A		intron	N/A	NP_060765.4
	CYREN	NM_001305630.2		c.174+20287G>T		intron	N/A	NP_001292559.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM140	ENST00000275767.3	TSL:1 MANE Select	c.-25+192C>A		intron	N/A	ENSP00000275767.2
	CYREN	ENST00000459937.5	TSL:1	n.356+20287G>T		intron	N/A
	TMEM140	ENST00000466307.1	TSL:5	n.76+192C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39449 AN: 152074 Hom.: 5751 Cov.: 33

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.275

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

GnomAD4 genome AF: 0.259 AC: 39457 AN: 152190 Hom.: 5750 Cov.: 33 AF XY: 0.262 AC XY: 19486 AN XY: 74400

African (AFR) AF: 0.153 AC: 6348 AN: 41556

American (AMR) AF: 0.331 AC: 5057 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 472 AN: 3472

East Asian (EAS) AF: 0.575 AC: 2965 AN: 5156

South Asian (SAS) AF: 0.176 AC: 851 AN: 4826

European-Finnish (FIN) AF: 0.310 AC: 3282 AN: 10594

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19641 AN: 67976

Other (OTH) AF: 0.277 AC: 583 AN: 2106

Alfa AF: 0.268 Hom.: 765

Bravo AF: 0.263

Asia WGS AF: 0.350 AC: 1214 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.7
DANN	Benign	0.52
PhyloP100		-0.85
PromoterAI		-0.052	Neutral
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: rs3735001; hg19: chr7-134833214;