NM_001031715.3:c.708A>G

Variant names:

• chr15-67357415-A-G
• rs374725274
• NM_001031715.3:c.708A>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001031715.3(IQCH):​c.708A>G​(p.Arg236Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,436,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: IQCH NM_001031715.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.222
• Publications: 0 publications found

Genes affected

IQCH (HGNC:25721): (IQ motif containing H)

IQCH-AS1 (HGNC:44104): (IQCH antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP7: Synonymous conserved (PhyloP=0.222 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031715.3. 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
	IQCH	NM_001031715.3	MANE Select	c.708A>G	p.Arg236Arg	synonymous	Exon 7 of 21	NP_001026885.2	Q86VS3-1
	IQCH	NM_001322475.2		c.189A>G	p.Arg63Arg	synonymous	Exon 5 of 18	NP_001309404.2
	IQCH	NM_001322470.2		c.189A>G	p.Arg63Arg	synonymous	Exon 4 of 16	NP_001309399.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IQCH	ENST00000335894.9	TSL:1 MANE Select	c.708A>G	p.Arg236Arg	synonymous	Exon 7 of 21	ENSP00000336861.4	Q86VS3-1
	IQCH	ENST00000629425.2	TSL:1	c.189A>G	p.Arg63Arg	synonymous	Exon 4 of 7	ENSP00000486970.1	Q86VS3-3
	IQCH	ENST00000514049.5	TSL:2	n.*191A>G		non_coding_transcript_exon	Exon 4 of 17	ENSP00000421223.1	D6RGG0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.96e-7 AC: 1 AN: 1436120 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 716102

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32918

American (AMR) AF: 0.00 AC: 0 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25994

East Asian (EAS) AF: 0.00 AC: 0 AN: 39562

South Asian (SAS) AF: 0.00 AC: 0 AN: 85720

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 9.19e-7 AC: 1 AN: 1088520

Other (OTH) AF: 0.00 AC: 0 AN: 59606

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.47
PhyloP100		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs374725274; hg19: chr15-67649753;