rs1111350

Variant names:

• chr10-101130664-G-A
• rs1111350
• ENST00000445873.5:n.341+122C>T

Variant summary

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

The ENST00000445873.5(TLX1NB):​n.341+122C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 180,148 control chromosomes in the GnomAD database, including 2,602 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 0.16 (2061 hom., cov: 32)
  • Exomes 𝑓: 0.19 (541 hom.)
• Consequence: TLX1NB ENST00000445873.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.954
• Publications: 2 publications found

Genes affected

TLX1NB (HGNC:37183): (TLX1 neighbor)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLX1NB	NR_130722.1	n.390+93C>T		intron_variant	Intron 1 of 2
TLX1NB	NR_130723.1	n.361+122C>T		intron_variant	Intron 1 of 2
TLX1NB	NR_130724.1	n.580-3566C>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLX1NB	ENST00000445873.5	n.341+122C>T		intron_variant	Intron 1 of 2	1
TLX1NB	ENST00000425505.2	n.405+93C>T		intron_variant	Intron 1 of 2	3
TLX1NB	ENST00000747503.1	n.732-3566C>T		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24191 AN: 152050 Hom.: 2057 Cov.: 32

Gnomad AFR AF: 0.0940

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.152

GnomAD4 exome AF: 0.188 AC: 5261 AN: 27980 Hom.: 541 Cov.: 0 AF XY: 0.190 AC XY: 2423 AN XY: 12762

African (AFR) AF: 0.123 AC: 115 AN: 932

American (AMR) AF: 0.205 AC: 126 AN: 614

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 264 AN: 1784

East Asian (EAS) AF: 0.286 AC: 1629 AN: 5692

South Asian (SAS) AF: 0.199 AC: 47 AN: 236

European-Finnish (FIN) AF: 0.278 AC: 5 AN: 18

Middle Eastern (MID) AF: 0.159 AC: 29 AN: 182

European-Non Finnish (NFE) AF: 0.164 AC: 2653 AN: 16226

Other (OTH) AF: 0.171 AC: 393 AN: 2296

GnomAD4 genome AF: 0.159 AC: 24209 AN: 152168 Hom.: 2061 Cov.: 32 AF XY: 0.165 AC XY: 12244 AN XY: 74386

African (AFR) AF: 0.0939 AC: 3899 AN: 41526

American (AMR) AF: 0.194 AC: 2963 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 568 AN: 3472

East Asian (EAS) AF: 0.252 AC: 1300 AN: 5168

South Asian (SAS) AF: 0.187 AC: 899 AN: 4820

European-Finnish (FIN) AF: 0.244 AC: 2579 AN: 10580

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11502 AN: 68006

Other (OTH) AF: 0.152 AC: 320 AN: 2108

Alfa AF: 0.166 Hom.: 3523

Bravo AF: 0.155

Asia WGS AF: 0.177 AC: 613 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.4
DANN	Benign	0.49
PhyloP100		0.95
Mutation Taster		=300/0	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: rs1111350; hg19: chr10-102890421;