Genetic Variant ENSG00000310339:n.248+4539A>G (chr18-49655298-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The XR_007066363.1(LOC105372112):n.179-6736A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. Note: XR_007066363.1 is not a MANE Select or MANE Plus Clinical transcript for LOC105372112; the reported annotation may differ from that of the MANE-designated reference transcript for this gene. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. 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: not found (cov: 31)

Consequence

LOC105372112
XR_007066363.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0150

Publications

79 publications found

Variant links:

Genes affected

ENSG00000310339 (HGNC:):

ENSG00000310339 links:

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new If you want to explore the variant's impact on the transcript XR_007066363.1, 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		Absent from gnomAD (AR/unknown gene) — PM2; Absent from gnomAD at well-covered site (MOI: unknown) (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: ENST00000849189.1. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

There are no transcript annotations for this variant.

Ensembl Transcripts

Gene / Transcript	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
ENSG00000310339 ENST00000849189.1	n.248+4539A>G	intron	Intron 1 of 3	Prot:
ENSG00000310339 ENST00000849192.1	n.232-1589A>G	intron	Intron 1 of 1	Prot:
ENSG00000310339 ENST00000849193.1	n.276-1589A>G	intron	Intron 1 of 1	Prot:

ENSG00000310339 ENST00000849189.1

HGVSc / HGVSpn.248+4539A>G

Exon rankIntron 1 of 3

intron

Prot:

ENSG00000310339 ENST00000849192.1

HGVSc / HGVSpn.232-1589A>G

Exon rankIntron 1 of 1

intron

Prot:

ENSG00000310339 ENST00000849193.1

HGVSc / HGVSpn.276-1589A>G

Exon rankIntron 1 of 1

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:	AC:	Hom:	AN:	Cov:31
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:31
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.00	AC:0	Hom:8852	AN:23468	Cov:

Showing 3 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score
AlphaGenome AVI	Benign	1.8
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.7
DANN	Benign	0.72
GPN-Star LLR	N/A	2.2
GPN-Star score	N/A	-2.2
PhyloP100	Benign	0.015

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