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GeneBe

1-27547334-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001371928.1(AHDC1):c.4782C>T(p.Pro1594=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.006 in 1,552,134 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0040 ( 3 hom., cov: 33)
Exomes 𝑓: 0.0062 ( 42 hom. )

Consequence

AHDC1
NM_001371928.1 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.43
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-27547334-G-A is Benign according to our data. Variant chr1-27547334-G-A is described in ClinVar as [Benign]. Clinvar id is 783928.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.42 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00404 (615/152328) while in subpopulation NFE AF= 0.00657 (447/68036). AF 95% confidence interval is 0.00607. There are 3 homozygotes in gnomad4. There are 269 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 611 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AHDC1NM_001371928.1 linkuse as main transcriptc.4782C>T p.Pro1594= synonymous_variant 8/9 ENST00000673934.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AHDC1ENST00000673934.1 linkuse as main transcriptc.4782C>T p.Pro1594= synonymous_variant 8/9 NM_001371928.1 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00401
AC:
611
AN:
152210
Hom.:
2
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00104
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00281
Gnomad ASJ
AF:
0.0161
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00248
Gnomad FIN
AF:
0.000188
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00657
Gnomad OTH
AF:
0.00336
GnomAD3 exomes
AF:
0.00392
AC:
778
AN:
198486
Hom.:
1
AF XY:
0.00381
AC XY:
405
AN XY:
106194
show subpopulations
Gnomad AFR exome
AF:
0.00116
Gnomad AMR exome
AF:
0.00295
Gnomad ASJ exome
AF:
0.0144
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00444
Gnomad FIN exome
AF:
0.000164
Gnomad NFE exome
AF:
0.00539
Gnomad OTH exome
AF:
0.00304
GnomAD4 exome
AF:
0.00621
AC:
8695
AN:
1399806
Hom.:
42
Cov.:
30
AF XY:
0.00608
AC XY:
4203
AN XY:
691522
show subpopulations
Gnomad4 AFR exome
AF:
0.00112
Gnomad4 AMR exome
AF:
0.00265
Gnomad4 ASJ exome
AF:
0.0150
Gnomad4 EAS exome
AF:
0.0000255
Gnomad4 SAS exome
AF:
0.00565
Gnomad4 FIN exome
AF:
0.000438
Gnomad4 NFE exome
AF:
0.00682
Gnomad4 OTH exome
AF:
0.00656
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00404
AC:
615
AN:
152328
Hom.:
3
Cov.:
33
AF XY:
0.00361
AC XY:
269
AN XY:
74492
show subpopulations
Gnomad4 AFR
AF:
0.00103
Gnomad4 AMR
AF:
0.00281
Gnomad4 ASJ
AF:
0.0161
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00331
Gnomad4 FIN
AF:
0.000188
Gnomad4 NFE
AF:
0.00657
Gnomad4 OTH
AF:
0.00332
Alfa
AF:
0.00465
Hom.:
2
Bravo
AF:
0.00404
Asia WGS
AF:
0.00115
AC:
4
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Benign, criteria provided, single submitterclinical testingGeneDxAug 21, 2018- -
Benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenMar 01, 2024AHDC1: BP4, BP7, BS1, BS2 -
Benign, criteria provided, single submitterclinical testingInvitaeJan 25, 2024- -
AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndrome Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabDec 05, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.67
Cadd
Benign
2.5
Dann
Benign
0.90

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs61742782; hg19: chr1-27873845; COSMIC: COSV55937478; COSMIC: COSV55937478; API