rs876657441

Variant names:

• chr19-44707853-C-T
• rs876657441
• NM_001039213.4:c.941-8C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001039213.4(CEACAM16):​c.941-8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,377,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: CEACAM16 NM_001039213.4 splice_region, intron
• Scores: Splicing: ADA: 0.00003401
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.978
• Publications: 0 publications found

Genes affected

CEACAM16 (HGNC:31948): (CEA cell adhesion molecule 16, tectorial membrane component) The protein encoded by this gene is a secreted glycoprotein that in mouse interacts with tectorial membrane proteins in the inner ear. The encoded adhesion protein is found in cochlear outer hair cells and appears to be important for proper hearing over an extended frequency range. Defects in this gene likely are a cause of non-syndromic autosomal dominant hearing loss. [provided by RefSeq, May 2012]

CEACAM16-AS1 (HGNC:55317): (CEACAM16, CEACAM19 and PVR antisense RNA 1)

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 19-44707853-C-T is Benign according to our data. Variant chr19-44707853-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 227243.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039213.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEACAM16	NM_001039213.4	MANE Select	c.941-8C>T		splice_region intron	N/A	NP_001034302.2	Q2WEN9
	CEACAM16-AS1	NR_186815.1		n.348-8676G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEACAM16	ENST00000587331.7	TSL:1 MANE Select	c.941-8C>T		splice_region intron	N/A	ENSP00000466561.1	Q2WEN9
	CEACAM16	ENST00000405314.2	TSL:5	c.941-8C>T		splice_region intron	N/A	ENSP00000385576.1	Q2WEN9
	CEACAM16-AS1	ENST00000590796.1	TSL:5	n.314+8097G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000145 AC: 2 AN: 1377800 Hom.: 0 Cov.: 29 AF XY: 0.00000148 AC XY: 1 AN XY: 673762

African (AFR) AF: 0.0000628 AC: 2 AN: 31842

American (AMR) AF: 0.00 AC: 0 AN: 38056

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21714

East Asian (EAS) AF: 0.00 AC: 0 AN: 37972

South Asian (SAS) AF: 0.00 AC: 0 AN: 73464

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49512

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4870

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1063644

Other (OTH) AF: 0.00 AC: 0 AN: 56726

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.6
DANN	Benign	0.64
PhyloP100		0.98

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000034
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.10		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs876657441; hg19: chr19-45211125;