rs878853068

Variant names:

• chr1-27603634-T-C
• rs878853068
• NM_001371928.1:c.-727+94A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001371928.1(AHDC1):​c.-727+94A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 22)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AHDC1 NM_001371928.1 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.381
• Publications: 0 publications found

Genes affected

AHDC1 (HGNC:25230): (AT-hook DNA binding motif containing 1) This gene encodes a protein containing two AT-hooks, which likely function in DNA binding. Mutations in this gene were found in individuals with Xia-Gibbs syndrome. [provided by RefSeq, Jun 2014]

AHDC1 Gene-Disease associations (from GenCC):

• AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Illumina, Orphanet, G2P, ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHDC1	NM_001371928.1	c.-727+94A>G		intron_variant	Intron 2 of 8	ENST00000673934.1	NP_001358857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHDC1	ENST00000673934.1	c.-727+94A>G		intron_variant	Intron 2 of 8		NM_001371928.1	ENSP00000501218.1

Frequencies

GnomAD3 genomes AF: 0.0000327 AC: 3 AN: 91624 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.0000422

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000225

Gnomad OTH AF: 0.000756

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 372 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 288

African (AFR) AF: 0.00 AC: 0 AN: 12

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 16

South Asian (SAS) AF: 0.00 AC: 0 AN: 16

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 14

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 288

Other (OTH) AF: 0.00 AC: 0 AN: 24

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000327 AC: 3 AN: 91624 Hom.: 0 Cov.: 22 AF XY: 0.0000227 AC XY: 1 AN XY: 44066

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

African (AFR) AF: 0.0000422 AC: 1 AN: 23688

American (AMR) AF: 0.00 AC: 0 AN: 9040

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2364

East Asian (EAS) AF: 0.00 AC: 0 AN: 2846

South Asian (SAS) AF: 0.00 AC: 0 AN: 2418

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 200

European-Non Finnish (NFE) AF: 0.0000225 AC: 1 AN: 44504

Other (OTH) AF: 0.000756 AC: 1 AN: 1322

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Feb 11, 2015

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	17
DANN	Benign	0.79
PhyloP100		0.38
PromoterAI		-0.024	Neutral

Splicing

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

Other links and lift over

dbSNP: rs878853068; hg19: chr1-27930145;