rs2805810

Positions:

• chr9-97569456-C-T

Variant summary

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

The NM_003275.4(TMOD1):​c.870+419C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 152,156 control chromosomes in the GnomAD database, including 4,241 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 0.23 (4241 hom., cov: 32)
• Consequence: TMOD1 NM_003275.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550

Genes affected

TMOD1 (HGNC:11871): (tropomodulin 1) This gene encodes a member of the tropomodulin family. The encoded protein is an actin-capping protein that regulates tropomyosin by binding to its N-terminus, inhibiting depolymerization and elongation of the pointed end of actin filaments and thereby influencing the structure of the erythrocyte membrane skeleton. Multiple transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMOD1	NM_003275.4	c.870+419C>T		intron_variant		ENST00000259365.9	NP_003266.1
TMOD1	NM_001166116.2	c.870+419C>T		intron_variant			NP_001159588.1
TMOD1	XM_047423825.1	c.462+419C>T		intron_variant			XP_047279781.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMOD1	ENST00000259365.9	c.870+419C>T		intron_variant		1	NM_003275.4	ENSP00000259365.3
TMOD1	ENST00000395211.6	c.870+419C>T		intron_variant		1		ENSP00000378637.2
TMOD1	ENST00000375175.1	c.489+419C>T		intron_variant		2		ENSP00000364318.1

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34540 AN: 152038 Hom.: 4230 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.0425

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.227 AC: 34592 AN: 152156 Hom.: 4241 Cov.: 32 AF XY: 0.229 AC XY: 17033 AN XY: 74388

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.185

Gnomad4 EAS AF: 0.0424

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.352

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.202

Alfa AF: 0.239 Hom.: 1105

Bravo AF: 0.211

Asia WGS AF: 0.163 AC: 567 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.4
DANN	Benign	0.37

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: rs2805810; hg19: chr9-100331738; COSMIC: COSV52251186;