rs3250

chr7-135160680-G-Achr7-135160680-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018295.5(TMEM140):c.-24-3738G>A 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 151,138 control chromosomes in the GnomAD database, including 17,524 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 (17524 hom., cov: 29)
• Consequence: TMEM140 NM_018295.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.193

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM140	NM_018295.5	c.-24-3738G>A		intron_variant		ENST00000275767.3
CYREN	NM_001305630.2	c.174+8069C>T		intron_variant
CYREN	XM_017012595.2	c.*40+7052C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM140	ENST00000275767.3	c.-24-3738G>A		intron_variant		1	NM_018295.5	P1
CYREN	ENST00000459937.5	n.356+8069C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72112 AN: 151022 Hom.: 17502 Cov.: 29

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.650

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.649

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.471

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

GnomAD4 genome AF: 0.478 AC: 72190 AN: 151138 Hom.: 17524 Cov.: 29 AF XY: 0.478 AC XY: 35232 AN XY: 73774

Gnomad4 AFR AF: 0.408

Gnomad4 AMR AF: 0.501

Gnomad4 ASJ AF: 0.650

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.650

Gnomad4 FIN AF: 0.480

Gnomad4 NFE AF: 0.509

Gnomad4 OTH AF: 0.474

Alfa AF: 0.442 Hom.: 2749

Bravo AF: 0.472

Asia WGS AF: 0.480 AC: 1667 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.1
Dann	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs3250; hg19: chr7-134845432;