rs7659526

Positions:

• chr4-105700486-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020395.4(INTS12):​c.-9-472A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 151,766 control chromosomes in the GnomAD database, including 5,948 homozygotes. 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: 𝑓 0.24 (5948 hom., cov: 31)
• Consequence: INTS12 NM_020395.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.194

Genes affected

INTS12 (HGNC:25067): (integrator complex subunit 12) INTS12 is a subunit of the Integrator complex, which associates with the C-terminal domain of RNA polymerase II large subunit (POLR2A; MIM 180660) and mediates 3-prime end processing of small nuclear RNAs U1 (RNU1; MIM 180680) and U2 (RNU2; MIM 180690) (Baillat et al., 2005 [PubMed 16239144]).[supplied by OMIM, Mar 2008]

LOC124900748 (HGNC:):

ARHGEF38 (HGNC:25968): (Rho guanine nucleotide exchange factor 38) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of catalytic activity. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INTS12	NM_020395.4	c.-9-472A>G		intron_variant		ENST00000340139.10
LOC124900748	XR_007058215.1	n.325+215T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INTS12	ENST00000340139.10	c.-9-472A>G		intron_variant		1	NM_020395.4	P1

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35713 AN: 151648 Hom.: 5924 Cov.: 31

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.0683

Gnomad SAS AF: 0.0856

Gnomad FIN AF: 0.0597

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.258

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.236 AC: 35782 AN: 151766 Hom.: 5948 Cov.: 31 AF XY: 0.229 AC XY: 16973 AN XY: 74200

Gnomad4 AFR AF: 0.475

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.229

Gnomad4 EAS AF: 0.0683

Gnomad4 SAS AF: 0.0854

Gnomad4 FIN AF: 0.0597

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.255

Alfa AF: 0.176 Hom.: 2996

Bravo AF: 0.263

Asia WGS AF: 0.111 AC: 385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	5.5
DANN	Benign	0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7659526; hg19: chr4-106621643;