chr3-57269450-A-AGAATT

Position:

• chr3-57269450-A-AGAATT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001142733.3(ASB14):​c.*190_*191insAATTC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 1,344,606 control chromosomes in the GnomAD database, including 31,841 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.28 (8546 hom., cov: 23)
  • Exomes 𝑓: 0.18 (23295 hom.)
• Consequence: ASB14 NM_001142733.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.853

Genes affected

ASB14 (HGNC:19766): (ankyrin repeat and SOCS box containing 14) The protein encoded by this gene is a member of the ankyrin repeat and SOCS box-containing (ASB) family of proteins. They contain ankyrin repeat sequence and a SOCS box domain. The SOCS box serves to couple suppressor of cytokine signalling (SOCS) proteins and their binding partners with the elongin B and C complex, possibly targeting them for degradation. Alternative splicing results in multiple transcript variants encoding different isoforms.[provided by RefSeq, Dec 2008]

APPL1 (HGNC:24035): (adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1) The protein encoded by this gene has been shown to be involved in the regulation of cell proliferation, and in the crosstalk between the adiponectin signalling and insulin signalling pathways. The encoded protein binds many other proteins, including RAB5A, DCC, AKT2, PIK3CA, adiponectin receptors, and proteins of the NuRD/MeCP1 complex. This protein is found associated with endosomal membranes, but can be released by EGF and translocated to the nucleus. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 3-57269450-A-AGAATT is Benign according to our data. Variant chr3-57269450-A-AGAATT is described in ClinVar as [Benign]. Clinvar id is 1235569.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASB14	NM_001142733.3	c.*190_*191insAATTC		3_prime_UTR_variant	11/11	ENST00000487349.6	NP_001136205.2
APPL1	NM_012096.3	c.1984-88_1984-87insTTGAA		intron_variant		ENST00000288266.8	NP_036228.1
ASB14	NM_130387.5	c.*190_*191insAATTC		3_prime_UTR_variant	4/4		NP_569058.1
APPL1	XM_011533583.4	c.1933-88_1933-87insTTGAA		intron_variant			XP_011531885.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASB14	ENST00000487349.6	c.*190_*191insAATTC		3_prime_UTR_variant	11/11	1	NM_001142733.3	ENSP00000419199	P1
APPL1	ENST00000288266.8	c.1984-88_1984-87insTTGAA		intron_variant		1	NM_012096.3	ENSP00000288266	P1
APPL1	ENST00000650354.1	c.1984-88_1984-87insTTGAA		intron_variant, NMD_transcript_variant				ENSP00000498115

Frequencies

GnomAD3 genomes AF: 0.277 AC: 41989 AN: 151726 Hom.: 8509 Cov.: 23

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.0545

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.241

GnomAD4 exome AF: 0.180 AC: 214379 AN: 1192762 Hom.: 23295 Cov.: 15 AF XY: 0.177 AC XY: 104853 AN XY: 593502

Gnomad4 AFR exome AF: 0.578

Gnomad4 AMR exome AF: 0.142

Gnomad4 ASJ exome AF: 0.0567

Gnomad4 EAS exome AF: 0.000610

Gnomad4 SAS exome AF: 0.114

Gnomad4 FIN exome AF: 0.177

Gnomad4 NFE exome AF: 0.185

Gnomad4 OTH exome AF: 0.184

GnomAD4 genome AF: 0.277 AC: 42071 AN: 151844 Hom.: 8546 Cov.: 23 AF XY: 0.271 AC XY: 20104 AN XY: 74242

Gnomad4 AFR AF: 0.574

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.0545

Gnomad4 EAS AF: 0.00231

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.239

Alfa AF: 0.239 Hom.: 646

Asia WGS AF: 0.0870 AC: 304 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 30, 2018

- -

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: rs10662232; hg19: chr3-57303478;