Genetic Variant ENSG00000254951:n.353+10438G>A (chr11-7895165-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is The variant received -2 classification points (ACMG Germline Pathogenicity v2019). PM2BP4_Strong

The NR_036678.1(LOC283299):n.353+10438G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. Note: NR_036678.1 is not a MANE Select or MANE Plus Clinical transcript for LOC283299; 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 0.00000658 (AC=1) in the gnomAD database across 151,976 control chromosomes (no homozygotes observed). The grpmax filtering allele frequency (95% CI) is 0.00000658. 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 0.0000066 ( 0 hom., cov: 32)

Consequence

LOC283299
NR_036678.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.410

Publications

2 publications found

Variant links:

Genes affected

ENSG00000254951 (HGNC:):

ENSG00000254951 links:

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new If you want to explore the variant's impact on the transcript NR_036678.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Likely_benign. The variant received -2 points.

Show applied only (2)

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM2Absent/extremely low in population databases		Very rare in gnomAD for AR/unknown gene (popmax AF < threshold/10) — PM2; GnomAD popmax AF = 0.00000658 — very rare for unknown gene (threshold 0.001) — PM2 moderate.
	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).

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NR_036678.1. 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
	LOC283299 NR_036678.1		n.353+10438G>A	intron	Intron 1 of 7	Prot:

LOC283299 NR_036678.1

HGVSc / HGVSpn.353+10438G>A

Exon rankIntron 1 of 7

intron

Prot:

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	ENSG00000254951 ENST00000527847.5	TSL:2	n.353+10438G>A	intron	Intron 1 of 7	Prot:
	ENSG00000254951 ENST00000718815.1		n.373+10438G>A	intron	Intron 2 of 2	Prot:

ENSG00000254951 ENST00000527847.5

TSL:2

HGVSc / HGVSpn.353+10438G>A

Exon rankIntron 1 of 7

intron

Prot:

ENSG00000254951 ENST00000718815.1

HGVSc / HGVSpn.373+10438G>A

Exon rankIntron 2 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 3 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.00000658	AC:1	Hom:0	AN:151976	Cov:32
GnomAD4 genome	AF: 0.00000658	AC:1	Hom:0	AN:151976	Cov:32
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.00	AC:0	Hom:2536	AN:114042	Cov:

Showing 3 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score
AlphaGenome AVI	Uncertain	12
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.73
GPN-Star LLR	N/A	0.18
GPN-Star score	N/A	-0.18
PhyloP100	Benign	-0.41

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.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational Scores

Splicing Scores

MaveDB functional evidence ?

Publications

Other links and lift over

MaveDB functional evidence