4-105685451-A-G

Position:

• chr4-105685451-A-G

Variant summary

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

The NM_020395.4(INTS12):​c.804+1241T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0536 in 152,260 control chromosomes in the GnomAD database, including 252 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 0.054 (252 hom., cov: 32)
• Consequence: INTS12 NM_020395.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0460

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]

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=-0.77).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INTS12	NM_020395.4	c.804+1241T>C		intron_variant		ENST00000340139.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INTS12	ENST00000340139.10	c.804+1241T>C		intron_variant		1	NM_020395.4	P1

Frequencies

GnomAD3 genomes AF: 0.0537 AC: 8168 AN: 152142 Hom.: 253 Cov.: 32

Gnomad AFR AF: 0.0407

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.0699

Gnomad ASJ AF: 0.0815

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0209

Gnomad FIN AF: 0.0318

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0641

Gnomad OTH AF: 0.0760

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

GnomAD4 genome AF: 0.0536 AC: 8166 AN: 152260 Hom.: 252 Cov.: 32 AF XY: 0.0511 AC XY: 3805 AN XY: 74440

Gnomad4 AFR AF: 0.0408

Gnomad4 AMR AF: 0.0697

Gnomad4 ASJ AF: 0.0815

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0209

Gnomad4 FIN AF: 0.0318

Gnomad4 NFE AF: 0.0642

Gnomad4 OTH AF: 0.0757

Alfa AF: 0.0529 Hom.: 25

Bravo AF: 0.0564

Asia WGS AF: 0.0140 AC: 49 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.7
DANN	Benign	0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs11726569; hg19: chr4-106606608;