rs3741219

Positions:

• chr11-1995389-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NR_131224.1(H19):​n.1026T>C 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Failed GnomAD Quality Control
• Consequence: H19 NR_131224.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.213

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:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
H19	NR_131224.1	n.1026T>C		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
H19	ENST00000710497.1	n.893T>C		non_coding_transcript_exon_variant	5/5

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD3 exomes AF: 0.418 AC: 95675 AN: 228728 Hom.: 21386 AF XY: 0.422 AC XY: 53335 AN XY: 126494

Gnomad AFR exome AF: 0.133

Gnomad AMR exome AF: 0.371

Gnomad ASJ exome AF: 0.498

Gnomad EAS exome AF: 0.325

Gnomad SAS exome AF: 0.291

Gnomad FIN exome AF: 0.520

Gnomad NFE exome AF: 0.501

Gnomad OTH exome AF: 0.452

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome Cov.: 0

Alfa AF: 0.468 Hom.: 3315

Asia WGS AF: 0.281 AC: 978 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	9.4
DANN	Benign	0.32

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3741219; hg19: chr11-2016619; COSMIC: COSV66403698;