19-7184640-GGAGAGAGAGAGA-GGA

Variant names:

• chr19-7184640-GGAGAGAGAGA-G
• NM_000208.4:c.653-13_653-4delTCTCTCTCTC

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_000208.4(INSR):​c.653-13_653-4delTCTCTCTCTC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000243 in 1,233,930 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000024 (0 hom.)
• Consequence: INSR NM_000208.4 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.04

Genes affected

INSR (HGNC:6091): (insulin receptor) This gene encodes a member of the receptor tyrosine kinase family of proteins. The encoded preproprotein is proteolytically processed to generate alpha and beta subunits that form a heterotetrameric receptor. Binding of insulin or other ligands to this receptor activates the insulin signaling pathway, which regulates glucose uptake and release, as well as the synthesis and storage of carbohydrates, lipids and protein. Mutations in this gene underlie the inherited severe insulin resistance syndromes including type A insulin resistance syndrome, Donohue syndrome and Rabson-Mendenhall syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 19-7184640-GGAGAGAGAGA-G is Benign according to our data. Variant chr19-7184640-GGAGAGAGAGA-G is described in ClinVar as [Likely_benign]. Clinvar id is 1943388.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INSR	NM_000208.4	c.653-13_653-4delTCTCTCTCTC		splice_region_variant, intron_variant	Intron 2 of 21	ENST00000302850.10	NP_000199.2
INSR	NM_001079817.3	c.653-13_653-4delTCTCTCTCTC		splice_region_variant, intron_variant	Intron 2 of 20		NP_001073285.1
INSR	XM_011527988.3	c.653-13_653-4delTCTCTCTCTC		splice_region_variant, intron_variant	Intron 2 of 21		XP_011526290.2
INSR	XM_011527989.4	c.653-13_653-4delTCTCTCTCTC		splice_region_variant, intron_variant	Intron 2 of 20		XP_011526291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INSR	ENST00000302850.10	c.653-13_653-4delTCTCTCTCTC		splice_region_variant, intron_variant	Intron 2 of 21	1	NM_000208.4	ENSP00000303830.4
INSR	ENST00000341500.9	c.653-13_653-4delTCTCTCTCTC		splice_region_variant, intron_variant	Intron 2 of 20	1		ENSP00000342838.4
INSR	ENST00000598216.1	n.628-13_628-4delTCTCTCTCTC		splice_region_variant, intron_variant	Intron 2 of 9	1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000243 AC: 3 AN: 1233930 Hom.: 0 AF XY: 0.00000485 AC XY: 3 AN XY: 617958

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000212

Gnomad4 NFE exome AF: 0.00000213

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 16, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-7184651;