8-144517775-G-C

Variant names:

• chr8-144517775-G-C
• rs878854640
• NM_004260.4:c.10C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004260.4(RECQL4):​c.10C>G​(p.Leu4Val) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L4L) 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 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.309
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24596477).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RECQL4	NM_004260.4	c.10C>G	p.Leu4Val	missense_variant	Exon 1 of 21	ENST00000617875.6	NP_004251.4
LRRC14	NM_014665.4	c.-378G>C		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.10C>G	p.Leu4Val	missense_variant	Exon 1 of 21	1	NM_004260.4	ENSP00000482313.2
LRRC14	ENST00000292524.6	c.-378G>C		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: 1111304 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 535782

African (AFR) AF: 0.00 AC: 0 AN: 22310

American (AMR) AF: 0.00 AC: 0 AN: 12408

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15802

East Asian (EAS) AF: 0.00 AC: 0 AN: 23538

South Asian (SAS) AF: 0.00 AC: 0 AN: 35070

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23108

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3006

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 932594

Other (OTH) AF: 0.00 AC: 0 AN: 43468

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.046	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	20
DANN	Benign	0.88
DEOGEN2	Benign	0.055	T
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.52	T
M_CAP	Uncertain	0.26	D
MetaRNN	Benign	0.25	T
PhyloP100		-0.31
PrimateAI	Pathogenic	0.87	D
Sift4G	Benign	0.10	T
Polyphen		0.98	D
Vest4		0.16
MVP		0.49
GERP RS		1.6
PromoterAI		0.075	Neutral
Varity_R		0.085
gMVP		0.14
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs878854640; hg19: chr8-145743159;