rs17376456

Variant names:

• chr5-94221997-A-G
• rs17376456
• NM_001145678.3:c.3711-67873T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001145678.3(KIAA0825):​c.3711-67873T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0874 in 152,136 control chromosomes in the GnomAD database, including 733 homozygotes. 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: 𝑓 0.087 (733 hom., cov: 32)
• Consequence: KIAA0825 NM_001145678.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0470
• Publications: 29 publications found

Genes affected

KIAA0825 (HGNC:28532): (KIAA0825)

KIAA0825 Gene-Disease associations (from GenCC):

• polydactyly, postaxial, type a10

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• postaxial polydactyly type A

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000286577 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA0825	NM_001145678.3	c.3711-67873T>C		intron_variant	Intron 20 of 20	ENST00000682413.1	NP_001139150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA0825	ENST00000682413.1	c.3711-67873T>C		intron_variant	Intron 20 of 20		NM_001145678.3	ENSP00000506760.1
KIAA0825	ENST00000703867.1	c.3726-67873T>C		intron_variant	Intron 20 of 20			ENSP00000515512.1
KIAA0825	ENST00000513200.7	c.3711-67873T>C		intron_variant	Intron 19 of 19	5		ENSP00000424618.2
ENSG00000286577	ENST00000745603.1	n.364+4536A>G		intron_variant	Intron 5 of 7

Frequencies

GnomAD3 genomes AF: 0.0874 AC: 13290 AN: 152018 Hom.: 734 Cov.: 32

Gnomad AFR AF: 0.0459

Gnomad AMI AF: 0.0670

Gnomad AMR AF: 0.0767

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.0457

Gnomad SAS AF: 0.0707

Gnomad FIN AF: 0.0289

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.110

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0874 AC: 13291 AN: 152136 Hom.: 733 Cov.: 32 AF XY: 0.0834 AC XY: 6206 AN XY: 74378

African (AFR) AF: 0.0458 AC: 1902 AN: 41508

American (AMR) AF: 0.0766 AC: 1170 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 667 AN: 3468

East Asian (EAS) AF: 0.0456 AC: 236 AN: 5172

South Asian (SAS) AF: 0.0710 AC: 342 AN: 4816

European-Finnish (FIN) AF: 0.0289 AC: 306 AN: 10598

Middle Eastern (MID) AF: 0.144 AC: 42 AN: 292

European-Non Finnish (NFE) AF: 0.123 AC: 8334 AN: 67992

Other (OTH) AF: 0.109 AC: 231 AN: 2110

Alfa AF: 0.112 Hom.: 3585

Bravo AF: 0.0890

Asia WGS AF: 0.0700 AC: 244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.39
PhyloP100		-0.047
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17376456; hg19: chr5-93557702; COSMIC: COSV70247317;