8-144517763-G-T

Variant names:

• chr8-144517763-G-T
• rs1554905170
• NM_004260.4:c.22C>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_004260.4(RECQL4):​c.22C>A​(p.Arg8Arg) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. R8R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RECQL4 NM_004260.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.288
• Publications: 0 publications found

Genes affected

RECQL4 (HGNC:9949): (RecQ like helicase 4) The protein encoded by this gene is a DNA helicase that belongs to the RecQ helicase family. DNA helicases unwind double-stranded DNA into single-stranded DNAs and may modulate chromosome segregation. This gene is predominantly expressed in thymus and testis. Mutations in this gene are associated with Rothmund-Thomson, RAPADILINO and Baller-Gerold syndromes. [provided by RefSeq, Jan 2010]

LRRC14 (HGNC:20419): (leucine rich repeat containing 14) This gene encodes a leucine-rich repeat-containing protein. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 8-144517763-G-T is Benign according to our data. Variant chr8-144517763-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1669798.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.288 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RECQL4	NM_004260.4	c.22C>A	p.Arg8Arg	synonymous_variant	Exon 1 of 21	ENST00000617875.6	NP_004251.4
LRRC14	NM_014665.4	c.-390G>T		upstream_gene_variant		ENST00000292524.6	NP_055480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RECQL4	ENST00000617875.6	c.22C>A	p.Arg8Arg	synonymous_variant	Exon 1 of 21	1	NM_004260.4	ENSP00000482313.2
LRRC14	ENST00000292524.6	c.-390G>T		upstream_gene_variant		1	NM_014665.4	ENSP00000292524.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1151648 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 559524

African (AFR) AF: 0.00 AC: 0 AN: 22922

American (AMR) AF: 0.00 AC: 0 AN: 14602

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16990

East Asian (EAS) AF: 0.00 AC: 0 AN: 24322

South Asian (SAS) AF: 0.00 AC: 0 AN: 43680

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3164

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 955010

Other (OTH) AF: 0.00 AC: 0 AN: 45584

GnomAD4 genome Cov.: 34

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Baller-Gerold syndrome Benign:1

Nov 20, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	10
DANN	Benign	0.84
PhyloP100		-0.29
PromoterAI		0.068	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1554905170; hg19: chr8-145743147;