4-112646005-G-GTT

Variant names:

• chr4-112646005-G-GTT
• rs5861107
• NM_016648.4:c.203-344_203-343dupTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_016648.4(LARP7):​c.203-344_203-343dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 150,724 control chromosomes in the GnomAD database, including 7,614 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.27 (7614 hom., cov: 23)
• Consequence: LARP7 NM_016648.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.297
• Publications: 0 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: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 4-112646005-G-GTT is Benign according to our data. Variant chr4-112646005-G-GTT is described in ClinVar as Benign. ClinVar VariationId is 1265867.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.552 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.203-344_203-343dupTT		intron	N/A	NP_057732.2	Q4G0J3-1
	LARP7	NM_001370974.1		c.203-344_203-343dupTT		intron	N/A	NP_001357903.1	A0A8Q3SHN7
	LARP7	NM_001370975.1		c.203-344_203-343dupTT		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.203-344_203-343dupTT		intron	N/A	ENSP00000344950.5	Q4G0J3-1
	LARP7	ENST00000509061.5	TSL:1	c.203-344_203-343dupTT		intron	N/A	ENSP00000422626.2	Q4G0J3-1
	LARP7	ENST00000509622.5	TSL:1	n.100-344_100-343dupTT		intron	N/A	ENSP00000422451.1	D6RBH8

Frequencies

GnomAD3 genomes AF: 0.272 AC: 40949 AN: 150608 Hom.: 7583 Cov.: 23

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.272 AC: 41040 AN: 150724 Hom.: 7614 Cov.: 23 AF XY: 0.273 AC XY: 20089 AN XY: 73568

African (AFR) AF: 0.503 AC: 20612 AN: 41006

American (AMR) AF: 0.249 AC: 3780 AN: 15174

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 735 AN: 3456

East Asian (EAS) AF: 0.570 AC: 2916 AN: 5120

South Asian (SAS) AF: 0.298 AC: 1427 AN: 4792

European-Finnish (FIN) AF: 0.124 AC: 1269 AN: 10242

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9524 AN: 67634

Other (OTH) AF: 0.265 AC: 556 AN: 2098

Alfa AF: 0.0470 Hom.: 35

ClinVar

ClinVar submissions

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
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs5861107; hg19: chr4-113567161;