Genetic Variant NM_001100420.2:c.727+46A>C (chr21-17795162-T-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001100420.2(C21orf91):c.727+46A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000947 in 1,056,344 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)

Exomes 𝑓: 9.5e-7 ( 0 hom. )

Consequence

C21orf91
NM_001100420.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.321

Publications

0 publications found

Variant links:

Genes affected

C21orf91 (HGNC:16459): (chromosome 21 open reading frame 91) Predicted to be involved in cerebral cortex neuron differentiation and positive regulation of dendritic spine development. [provided by Alliance of Genome Resources, Apr 2022]

C21orf91 links:

ENSG00000244676 (HGNC:):

ENSG00000244676 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
C21orf91	NM_001100420.2 link	c.727+46A>C	intron_variant	Intron 4 of 4	ENST00000284881.9	NP_001093890.1	Q9NYK6-1Q68DA1
C21orf91	NM_017447.4 link	c.727+46A>C	intron_variant	Intron 4 of 4		NP_059143.3	Q9NYK6-3Q68DA1
C21orf91	NM_001100421.2 link	c.664+1420A>C	intron_variant	Intron 3 of 3		NP_001093891.1	Q9NYK6-2Q68DA1
LOC124900465	XR_007067823.1 link	n.1605+38373T>G	intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C21orf91	ENST00000284881.9 link	c.727+46A>C		intron_variant	Intron 4 of 4	2	NM_001100420.2	ENSP00000284881.4		Q9NYK6-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.47e-7

AC:

AN:

1056344

Hom.:

Cov.:

AF XY:

0.00000184

AC XY:

AN XY:

544698

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25880

American (AMR)

AF:

0.00

AC:

AN:

44178

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23576

East Asian (EAS)

AF:

0.00

AC:

AN:

37884

South Asian (SAS)

AF:

0.00

AC:

AN:

77934

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52222

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4936

European-Non Finnish (NFE)

AF:

0.00000135

AC:

AN:

742696

Other (OTH)

AF:

0.00

AC:

AN:

47038

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.9

(source)

DANN

Benign

0.70

PhyloP100

-0.32

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over