rs543556010

Variant names:

• chr19-7112336-CA-C
• rs543556010
• NM_000208.4:c.*4719delT

Your query was ambiguous. Multiple possible variants found:

• chr19-7112336-CA-C
• chr19-7112336-CA-CAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_000208.4(INSR):​c.*4719delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00334 in 150,154 control chromosomes in the GnomAD database, including 4 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0033 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: INSR NM_000208.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.598

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 Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00334 (502/150154) while in subpopulation AFR AF= 0.0107 (439/40934). AF 95% confidence interval is 0.0099. There are 4 homozygotes in gnomad4. There are 238 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INSR	NM_000208.4	c.*4719delT		3_prime_UTR_variant	Exon 22 of 22	ENST00000302850.10	NP_000199.2
INSR	NM_001079817.3	c.*4719delT		3_prime_UTR_variant	Exon 21 of 21		NP_001073285.1
INSR	XM_011527988.3	c.*4719delT		3_prime_UTR_variant	Exon 22 of 22		XP_011526290.2
INSR	XM_011527989.4	c.*4719delT		3_prime_UTR_variant	Exon 21 of 21		XP_011526291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INSR	ENST00000302850	c.*4719delT		3_prime_UTR_variant	Exon 22 of 22	1	NM_000208.4	ENSP00000303830.4
INSR	ENST00000341500	c.*4719delT		3_prime_UTR_variant	Exon 21 of 21	1		ENSP00000342838.4

Frequencies

GnomAD3 genomes AF: 0.00334 AC: 501 AN: 150040 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0108

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00146

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000583

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000445

Gnomad OTH AF: 0.00341

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 FIN exome AF: 0.00

GnomAD4 genome AF: 0.00334 AC: 502 AN: 150154 Hom.: 4 Cov.: 32 AF XY: 0.00325 AC XY: 238 AN XY: 73260

Gnomad4 AFR AF: 0.0107

Gnomad4 AMR AF: 0.00146

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000585

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000445

Gnomad4 OTH AF: 0.00386

Bravo AF: 0.00349

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs543556010; hg19: chr19-7112347;