NM_018295.5:c.-24-5195A>G

Variant names:

• chr7-135159223-A-G
• rs1035695
• NM_018295.5:c.-24-5195A>G

Variant summary

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

The NM_018295.5(TMEM140):​c.-24-5195A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 152,094 control chromosomes in the GnomAD database, including 17,737 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 0.48 (17737 hom., cov: 33)
• Consequence: TMEM140 NM_018295.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347
• Publications: 7 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.63 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.-24-5195A>G		intron	N/A	NP_060765.4
	CYREN	NM_001305630.2		c.174+9526T>C		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.-24-5195A>G		intron	N/A	ENSP00000275767.2
	CYREN	ENST00000459937.5	TSL:1	n.356+9526T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72692 AN: 151976 Hom.: 17715 Cov.: 33

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.473

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

GnomAD4 genome AF: 0.478 AC: 72771 AN: 152094 Hom.: 17737 Cov.: 33 AF XY: 0.478 AC XY: 35568 AN XY: 74348

African (AFR) AF: 0.409 AC: 16959 AN: 41464

American (AMR) AF: 0.501 AC: 7667 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.652 AC: 2262 AN: 3470

East Asian (EAS) AF: 0.240 AC: 1244 AN: 5174

South Asian (SAS) AF: 0.649 AC: 3129 AN: 4822

European-Finnish (FIN) AF: 0.482 AC: 5096 AN: 10574

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.510 AC: 34654 AN: 67974

Other (OTH) AF: 0.475 AC: 1004 AN: 2114

Alfa AF: 0.485 Hom.: 2982

Bravo AF: 0.473

Asia WGS AF: 0.481 AC: 1671 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.5
DANN	Benign	0.69
PhyloP100		0.35
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: rs1035695; hg19: chr7-134843975;