ENST00000616341.1:n.98+35736G>A

Variant names:

• chr17-36900828-C-T
• rs8074144
• ENST00000616341.1:n.98+35736G>A

GermlineCancer (beta)

Variant summary

Our verdict is Benign.

<-10 Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

The ENST00000616341.1(LHX1-DT):n.98+35736G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. Note: ENST00000616341.1 is not a MANE Select or MANE Plus Clinical transcript for LHX1-DT; the reported annotation may differ from that of the MANE-designated reference transcript for this gene. The variant allele was found at a cumulative frequency of 0.189 (AC=28,772) in the gnomAD database across 152,138 control chromosomes, including 2,903 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.209. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (2903 hom., cov: 33)
• Consequence: LHX1-DT ENST00000616341.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.331
• Publications: 5 publications found

Genes affected

LHX1-DT (HGNC:53778): ()

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

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

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); No splicing predictor data available.; Germline computational verdict: benign (Strong).
	BA1Stand-alone benign allele frequency (>5%)		GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.2087 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: ENST00000616341.1. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	LHX1-DT NR_135671.1		n.98+35736G>A	intron	Intron 1 of 2	Prot:

LHX1-DT NR_135671.1

HGVSc / HGVSpn.98+35736G>A

Exon rankIntron 1 of 2

intron

Prot:

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	LHX1-DT ENST00000616341.1	TSL:2	n.98+35736G>A	intron	Intron 1 of 2	Prot:

LHX1-DT ENST00000616341.1

TSL:2

HGVSc / HGVSpn.98+35736G>A

Exon rankIntron 1 of 2

intron

Prot:

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 4 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.189	AC:28755	Hom:2900	AN:152020	Cov:33
GnomAD4 genome	AF: 0.189	AC:28772	Hom:2903	AN:152138	Cov:33
TOPMed (Bravo)	AF: 0.184	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.195	AC:41405	Hom:4194	AN:212520	Cov:
Local & regional cohorts 8 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.185	AC:433	Hom:41	AN:2342	Cov:
Denmark Genome	AF: 0.257	AC:77	Hom:	AN:300	Cov:
GenomeAsia100K	AF: 0.0750	AC:261	Hom:	AN:3478	Cov:
Korea4K (4,157 Koreans)	AF: 0.00871	AC:63	Hom:	AN:7234	Cov:
Qatari Genome	AF: 0.0966	AC:17	Hom:	AN:176	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.0275	AC:3379	Hom:54	AN:122656	Cov:
UK10K	AF: 0.210	AC:1589	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.0114	AC:102	Hom:1	AN:8960	Cov:

Showing 12 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	2.5
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.6
DANN	Benign	0.66
GPN-Star LLR	N/A	-0.55
GPN-Star score	N/A	0.55
PhyloP100	Benign	-0.33

Showing 7 of 7 scores

Splicing Scores

No splicing scores have been computed for this variant.

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs8074144;

hg19: chr17-35258114;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar