11-1996431-G-A

Variant names:

• chr11-1996431-G-A
• rs747425680
• ENST00000412788.6:n.1326-10C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP6

The ENST00000447298.3(H19):​n.756C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency: Genomes: not found (cov: 0)
• Consequence: H19 ENST00000447298.3 non_coding_transcript_exon
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.210
• Publications: 0 publications found

Genes affected

H19 (HGNC:4713): (H19 imprinted maternally expressed transcript) This gene is located in an imprinted region of chromosome 11 near the insulin-like growth factor 2 (IGF2) gene. This gene is only expressed from the maternally-inherited chromosome, whereas IGF2 is only expressed from the paternally-inherited chromosome. The product of this gene is a long non-coding RNA which functions as a tumor suppressor. Mutations in this gene have been associated with Beckwith-Wiedemann Syndrome and Wilms tumorigenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

MRPL23 (HGNC:10322): (mitochondrial ribosomal protein L23) Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 39S subunit protein. The gene is biallelically expressed, despite its location within a region of imprinted genes on chromosome 11. [provided by RefSeq, Jul 2008]

ENSG00000275266 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 11-1996431-G-A is Benign according to our data. Variant chr11-1996431-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3055295.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL23	NM_001400176.1	c.498-15110G>A		intron_variant	Intron 5 of 6		NP_001387105.1
H19	NR_002196.3	n.1326-10C>T		intron_variant	Intron 1 of 4
H19	NR_131223.2	n.1326-10C>T		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
H19	ENST00000412788.6	n.1326-10C>T		intron_variant	Intron 1 of 4	1
H19	ENST00000414790.11	n.1326-10C>T		intron_variant	Intron 1 of 4	1
H19	ENST00000447298.3	n.756C>T		non_coding_transcript_exon_variant	Exon 1 of 4	2

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD2 exomes AF: 0.000263 AC: 58 AN: 220356 AF XY: 0.000196

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000475

Gnomad NFE exome AF: 0.000514

Gnomad OTH exome AF: 0.000177

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

Alfa AF: 0.00112 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

H19-related disorder Benign:1

May 01, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.7
DANN	Benign	0.85
PhyloP100		-0.21

Splicing

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

Other links and lift over

dbSNP: rs747425680; hg19: chr11-2017661;