4-112645135-T-C

Variant names:

• chr4-112645135-T-C
• rs12650431
• NM_016648.4:c.202+264T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_016648.4(LARP7):​c.202+264T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.682 in 151,334 control chromosomes in the GnomAD database, including 35,667 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.68 (35667 hom., cov: 27)
• Consequence: LARP7 NM_016648.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.22
• Publications: 4 publications found

Genes affected

LARP7 (HGNC:24912): (La ribonucleoprotein 7, transcriptional regulator) This gene encodes a protein which is found in the 7SK snRNP (small nuclear ribonucleoprotein). This snRNP complex inhibits a cyclin-dependent kinase, positive transcription elongation factor b, which is required for paused RNA polymerase II at a promoter to begin transcription elongation. A pseudogene of this gene is located on chromosome 3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2012]

LARP7 Gene-Disease associations (from GenCC):

• microcephalic primordial dwarfism, Alazami type

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.06).
• BP6: Variant 4-112645135-T-C is Benign according to our data. Variant chr4-112645135-T-C is described in ClinVar as Benign. ClinVar VariationId is 1273157.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.937 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016648.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LARP7	NM_016648.4	MANE Select	c.202+264T>C		intron	N/A	NP_057732.2	Q4G0J3-1
	LARP7	NM_001370974.1		c.202+264T>C		intron	N/A	NP_001357903.1	A0A8Q3SHN7
	LARP7	NM_001370975.1		c.202+264T>C		intron	N/A	NP_001357904.1	A0A8Q3SHN7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LARP7	ENST00000344442.10	TSL:2 MANE Select	c.202+264T>C		intron	N/A	ENSP00000344950.5	Q4G0J3-1
	LARP7	ENST00000509061.5	TSL:1	c.202+264T>C		intron	N/A	ENSP00000422626.2	Q4G0J3-1
	LARP7	ENST00000509622.5	TSL:1	n.99+367T>C		intron	N/A	ENSP00000422451.1	D6RBH8

Frequencies

GnomAD3 genomes AF: 0.682 AC: 103143 AN: 151216 Hom.: 35626 Cov.: 27

Gnomad AFR AF: 0.657

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.758

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.959

Gnomad SAS AF: 0.803

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.683

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

GnomAD4 genome AF: 0.682 AC: 103247 AN: 151334 Hom.: 35667 Cov.: 27 AF XY: 0.686 AC XY: 50717 AN XY: 73894

African (AFR) AF: 0.657 AC: 27098 AN: 41234

American (AMR) AF: 0.758 AC: 11553 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 2238 AN: 3464

East Asian (EAS) AF: 0.959 AC: 4924 AN: 5132

South Asian (SAS) AF: 0.804 AC: 3855 AN: 4794

European-Finnish (FIN) AF: 0.657 AC: 6841 AN: 10408

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.659 AC: 44638 AN: 67770

Other (OTH) AF: 0.686 AC: 1440 AN: 2100

Alfa AF: 0.652 Hom.: 4205

Bravo AF: 0.691

Asia WGS AF: 0.884 AC: 3073 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.6
DANN	Benign	0.25
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12650431; hg19: chr4-113566291;