chr15-67372272-C-T

Variant names:

• chr15-67372272-C-T
• rs34738407
• NM_001031715.3:c.915C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_001031715.3(IQCH):​c.915C>T​(p.Val305Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000384 in 1,613,954 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0020 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00022 (0 hom.)
• Consequence: IQCH NM_001031715.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.03
• Publications: 1 publications found

Genes affected

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

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

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 15-67372272-C-T is Benign according to our data. Variant chr15-67372272-C-T is described in ClinVar as Benign. ClinVar VariationId is 722880.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.03 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.915C>T	p.Val305Val	synonymous	Exon 9 of 21	NP_001026885.2	Q86VS3-1
	IQCH	NM_001322475.2		c.396C>T	p.Val132Val	synonymous	Exon 7 of 18	NP_001309404.2
	IQCH	NM_001322470.2		c.396C>T	p.Val132Val	synonymous	Exon 6 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.915C>T	p.Val305Val	synonymous	Exon 9 of 21	ENSP00000336861.4	Q86VS3-1
	IQCH	ENST00000629425.2	TSL:1	c.396C>T	p.Val132Val	synonymous	Exon 6 of 7	ENSP00000486970.1	Q86VS3-3
	IQCH	ENST00000514049.5	TSL:2	n.*504C>T		non_coding_transcript_exon	Exon 7 of 17	ENSP00000421223.1	D6RGG0

Frequencies

GnomAD3 genomes AF: 0.00197 AC: 300 AN: 152000 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00667

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000852

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00527

GnomAD2 exomes AF: 0.000514 AC: 129 AN: 251028 AF XY: 0.000332

Gnomad AFR exome AF: 0.00683

Gnomad AMR exome AF: 0.000376

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000353

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000219 AC: 320 AN: 1461836 Hom.: 0 Cov.: 32 AF XY: 0.000183 AC XY: 133 AN XY: 727220

African (AFR) AF: 0.00786 AC: 263 AN: 33478

American (AMR) AF: 0.000380 AC: 17 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39694

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000162 AC: 18 AN: 1111984

Other (OTH) AF: 0.000315 AC: 19 AN: 60396

GnomAD4 genome AF: 0.00197 AC: 300 AN: 152118 Hom.: 1 Cov.: 32 AF XY: 0.00190 AC XY: 141 AN XY: 74362

African (AFR) AF: 0.00665 AC: 276 AN: 41490

American (AMR) AF: 0.000851 AC: 13 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67996

Other (OTH) AF: 0.00521 AC: 11 AN: 2110

Alfa AF: 0.00127 Hom.: 0

Bravo AF: 0.00239

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.097
DANN	Benign	0.40
PhyloP100		-3.0
PromoterAI		-0.011	Neutral
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs34738407; hg19: chr15-67664610; COSMIC: COSV100246282; COSMIC: COSV100246282;