1-211941865-A-T

Position:

• chr1-211941865-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015434.4(INTS7):​c.2848T>A​(p.Leu950Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: INTS7 NM_015434.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.25

Genes affected

INTS7 (HGNC:24484): (integrator complex subunit 7) This gene encodes a subunit of the integrator complex. The integrator complex associates with the C-terminal domain of RNA polymerase II and mediates 3'-end processing of the small nuclear RNAs U1 and U2. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

INTS7 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.026423663).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INTS7	NM_015434.4	c.2848T>A	p.Leu950Ile	missense_variant	20/20	ENST00000366994.8	NP_056249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INTS7	ENST00000366994.8	c.2848T>A	p.Leu950Ile	missense_variant	20/20	1	NM_015434.4	ENSP00000355961.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 09, 2024

The c.2848T>A (p.L950I) alteration is located in exon 20 (coding exon 20) of the INTS7 gene. This alteration results from a T to A substitution at nucleotide position 2848, causing the leucine (L) at amino acid position 950 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	11
DANN	Benign	0.88
DEOGEN2	Benign	0.014	T;.;.;.;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.78	T;T;T;T;T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.026	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.69	N;.;.;.;.
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.030	N;N;N;N;.
REVEL	Benign	0.054
Sift	Benign	0.36	T;T;T;T;.
Sift4G	Benign	0.50	T;T;T;T;T
Polyphen		0.062	B;B;B;.;.
Vest4		0.22
MutPred		0.13		Gain of MoRF binding (P = 0.089);.;.;.;.;
MVP		0.30
MPC		0.20
ClinPred		0.49	T
GERP RS		-0.38
Varity_R		0.056
gMVP		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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: chr1-212115207;