4-127633249-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015693.4(INTU):c.146+69G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 1,518,026 control chromosomes in the GnomAD database, including 177,914 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.46 (16340 hom., cov: 32)
  • Exomes 𝑓: 0.48 (161574 hom.)
• Consequence: INTU NM_015693.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.501

Genes affected

INTU (HGNC:29239): (inturned planar cell polarity protein) Involved in embryonic digit morphogenesis; roof of mouth development; and tongue morphogenesis. Located in ciliary basal body and motile cilium. Implicated in asphyxiating thoracic dystrophy and orofaciodigital syndrome XVII. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 4-127633249-G-A is Benign according to our data. Variant chr4-127633249-G-A is described in ClinVar as [Benign]. Clinvar id is 1294771.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INTU	NM_015693.4	c.146+69G>A		intron_variant		ENST00000335251.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INTU	ENST00000335251.11	c.146+69G>A		intron_variant		1	NM_015693.4	P1
INTU	ENST00000503952.5	c.146+69G>A		intron_variant, NMD_transcript_variant		1
INTU	ENST00000504491.1	c.89+9758G>A		intron_variant		4
INTU	ENST00000503626.5	c.146+69G>A		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69664 AN: 151868 Hom.: 16325 Cov.: 32

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.536

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.511

GnomAD4 exome AF: 0.482 AC: 658072 AN: 1366040 Hom.: 161574 AF XY: 0.488 AC XY: 328461 AN XY: 673706

Gnomad4 AFR exome AF: 0.414

Gnomad4 AMR exome AF: 0.422

Gnomad4 ASJ exome AF: 0.537

Gnomad4 EAS exome AF: 0.231

Gnomad4 SAS exome AF: 0.642

Gnomad4 FIN exome AF: 0.395

Gnomad4 NFE exome AF: 0.486

Gnomad4 OTH exome AF: 0.487

GnomAD4 genome AF: 0.459 AC: 69704 AN: 151986 Hom.: 16340 Cov.: 32 AF XY: 0.457 AC XY: 33961 AN XY: 74288

Gnomad4 AFR AF: 0.426

Gnomad4 AMR AF: 0.470

Gnomad4 ASJ AF: 0.536

Gnomad4 EAS AF: 0.272

Gnomad4 SAS AF: 0.625

Gnomad4 FIN AF: 0.395

Gnomad4 NFE AF: 0.483

Gnomad4 OTH AF: 0.514

Alfa AF: 0.497 Hom.: 24970

Bravo AF: 0.458

Asia WGS AF: 0.472 AC: 1642 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	3.6
Dann	Benign	0.87

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

Publications

LitVar

Other links and lift over

dbSNP: rs2255457; hg19: chr4-128554404; COSMIC: COSV56540271;