4-38772244-G-T

Variant names:

• chr4-38772244-G-T
• rs4504265
• NM_030956.4:c.*911C>A

Variant summary

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

The NM_030956.4(TLR10):​c.*911C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 152,106 control chromosomes in the GnomAD database, including 4,599 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 (4599 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: TLR10 NM_030956.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.342
• Publications: 6 publications found

Genes affected

TLR10 (HGNC:15634): (toll like receptor 10) The protein encoded by this gene is a member of the Toll-like receptor (TLR) family which plays a fundamental role in pathogen recognition and activation of innate immunity. TLRs are highly conserved from Drosophila to humans and share structural and functional similarities. They recognize pathogen-associated molecular patterns (PAMPs) that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity. The various TLRs exhibit different patterns of expression. This gene is most highly expressed in lymphoid tissues such as spleen, lymph node, thymus, and tonsil. Multiple alternatively spliced transcript variants which encode different protein isoforms have been found for this gene. [provided by RefSeq, Aug 2010]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLR10	NM_030956.4	c.*911C>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000308973.9	NP_112218.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLR10	ENST00000308973.9	c.*911C>A		3_prime_UTR_variant	Exon 4 of 4	5	NM_030956.4	ENSP00000308925.4
TLR10	ENST00000361424.6	c.*911C>A		3_prime_UTR_variant	Exon 2 of 2	1		ENSP00000354459.2
TLR10	ENST00000613579.4	c.*911C>A		3_prime_UTR_variant	Exon 3 of 3	3		ENSP00000478206.1
TLR10	ENST00000622002.4	c.*911C>A		3_prime_UTR_variant	Exon 3 of 3	3		ENSP00000478985.1

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35452 AN: 151986 Hom.: 4594 Cov.: 32

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.0962

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.290

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.233 AC: 35468 AN: 152106 Hom.: 4599 Cov.: 32 AF XY: 0.231 AC XY: 17188 AN XY: 74364

African (AFR) AF: 0.232 AC: 9621 AN: 41494

American (AMR) AF: 0.308 AC: 4701 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1344 AN: 3472

East Asian (EAS) AF: 0.428 AC: 2213 AN: 5174

South Asian (SAS) AF: 0.336 AC: 1622 AN: 4822

European-Finnish (FIN) AF: 0.0962 AC: 1017 AN: 10576

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 14003 AN: 67980

Other (OTH) AF: 0.287 AC: 604 AN: 2108

Alfa AF: 0.214 Hom.: 496

Bravo AF: 0.250

Asia WGS AF: 0.309 AC: 1074 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.1
DANN	Benign	0.58
PhyloP100		0.34
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: rs4504265; hg19: chr4-38773865;