rs2805810

Variant names:

• chr9-97569456-C-T
• rs2805810
• NM_003275.4:c.870+419C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TMOD1	NM_003275.4	c.870+419C>T		intron_variant	Intron 8 of 9	ENST00000259365.9	NP_003266.1
TMOD1	NM_001166116.2	c.870+419C>T		intron_variant	Intron 8 of 9		NP_001159588.1
TMOD1	XM_047423825.1	c.462+419C>T		intron_variant	Intron 6 of 7		XP_047279781.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMOD1	ENST00000259365.9	c.870+419C>T		intron_variant	Intron 8 of 9	1	NM_003275.4	ENSP00000259365.3
TMOD1	ENST00000395211.6	c.870+419C>T		intron_variant	Intron 8 of 9	1		ENSP00000378637.2
TMOD1	ENST00000375175.1	c.489+419C>T		intron_variant	Intron 5 of 6	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

African (AFR) AF: 0.182 AC: 7552 AN: 41508

American (AMR) AF: 0.197 AC: 3014 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 641 AN: 3472

East Asian (EAS) AF: 0.0424 AC: 220 AN: 5190

South Asian (SAS) AF: 0.200 AC: 964 AN: 4826

European-Finnish (FIN) AF: 0.352 AC: 3727 AN: 10574

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17695 AN: 67972

Other (OTH) AF: 0.202 AC: 428 AN: 2116

Alfa AF: 0.246 Hom.: 6329

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
PhyloP100		0.055
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: rs2805810; hg19: chr9-100331738; COSMIC: COSV52251186;